Unit 5- Cell Interactions and Signal Transduction.ppt

UNIT 5- CELL INTERACTIONS AND
SIGNAL TRANSDUCTION Dr. P. Deepak

CELL INTERACTIONS AND SIGNAL
TRANSDUCTION
Junction between cells – desmosomes, plasmodesmata;
synapse, gap and tight junctions; Cell to cell adhesion;
Chemical signalling in unicellular organisms and between
cells in higher organisms; Cell surface and intracellular
receptors and their role in signal mediation (general
information); Importance of second messengers in signal
transduction (cAMP, cGMP, calcium ions, phosphatidyl
inositol, phytohormones).

CELL INTERACTIONS
Cell signalling, also known as cell communication
or signal transduction, is the process by which cells
communicate with each other to coordinate their
activities and respond to their environment. It is a
crucial aspect of cellular function, allowing cells to
sense changes in their surroundings and
appropriately adjust their behavior and function in
response.

Cell signaling involves the transmission of molecular
signals from one cell to another,
it can occur through various mechanisms, including direct
cell-to-cell contact, secretion of signaling molecules, and
the detection of extracellular matrix components.
These signals are received and interpreted by
specialized proteins known as receptors on the surface or
inside the target cells.

THERE ARE THREE MAIN TYPES OF CELL
SIGNALLING:

AUTOCRINE SIGNALLING:
In autocrine signalling, a cell produces signalling
molecules that bind to receptors on its own surface,
leading to a response within the same cell. This
process is often associated with the regulation of
cell growth and differentiation.

Unit 5- Cell Interactions and Signal Transduction.ppt

PARACRINE SIGNALLING
Paracrine signalling: In paracrine signalling, cells
release signalling molecules into the extracellular
fluid, where they only affect nearby target cells.
These target cells have specific receptors for the
signalling molecules and respond accordingly.
Paracrine signalling is common in the nervous system
and in the immune response.

ENDOCRINE SIGNALLING
Endocrine signalling: In endocrine signalling,
specialized cells release signalling molecules (hormones)
into the bloodstream.
These hormones travel through the bloodstream to distant
target cells, which possess the appropriate receptors for
the specific hormones.
Endocrine signalling plays a crucial role in coordinating
processes throughout the entire body.

THE KEY COMPONENTS OF CELL
SIGNALLING INCLUDE
Signalling molecules
Receptors

SIGNAL TRANSDUCTION
Signal transduction is a fundamental process in biology that
refers to the transmission of signals from the external
environment or neighboring cells to the interior of a cell,
ultimately leading to a cellular response.
This mechanism allows cells to sense changes in their
surroundings and adapt their behavior accordingly.
Signal transduction is critical for various cellular processes,
including growth, development, immune responses, and
metabolism.

THE PROCESS OF SIGNAL TRANSDUCTION
GENERALLY INVOLVES THE FOLLOWING STEPS:

JUNCTION BETWEEN CELLS
The junctions between cells are specialized structures that
facilitate cell-to-cell communication, adhesion, and coordination
of cellular activities. These junctions are essential for the
organization and function of tissues in multicellular organisms.
There are three main types of cell junctions:
Tight junctions, (Occluding Junction)
Adherens junctions, (Anchoring Junction) &
Gap junctions (Communicating Junction).

TIGHT JUNCTIONS:
Tight junctions, also known as occluding junctions, form a barrier between
adjacent cells, preventing the movement of substances between the cells.
They are commonly found in epithelial tissues, such as the lining of the
intestines and blood vessels.
Tight junctions consist of transmembrane proteins, such as claudins and
occludins, that interact with complementary proteins on adjacent cells.
The tight junctions effectively seal the space between cells, controlling the
passage of ions, water, and molecules, and ensuring the proper
functioning of selective permeability.
Apical surface –carrier proteins
Basolateral surface-carrier
proteins

ADHERENS JUNCTIONS:
Adherens junctions play a role in cell adhesion and tissue integrity.
They are typically found just below tight junctions in epithelial tissues.
Adherens junctions are formed by cadherin proteins that interact with
cadherins on neighboring cells.
The cadherins are linked to the actin cytoskeleton inside the cell,
providing structural support and allowing the transmission of mechanical
forces between cells.
Adherens junctions contribute to the overall strength and stability of
tissues.

GAP JUNCTIONS:
Gap junctions facilitate direct communication between adjacent cells.
They are composed of connexin proteins, which form small channels
called connexons. These channels allow the passage of ions, small
molecules, and signalling molecules between the cytoplasm of
connected cells.
Gap junctions are essential for coordinating activities among cells in
tissues like cardiac muscle and nervous tissue. They enable electrical
and biochemical coupling, enabling rapid communication and
synchronization of cellular responses.

Connexin 43- cataract in mice
Connexin 37- signals to reach eggs to mature
Connexin 46 – lens transparancy

DESMOSOMES
Desmosomes, also known as macula adherens, are specialized cell
junctions that provide strong mechanical adhesion between cells in
tissues subjected to mechanical stress.
These junctions are commonly found in tissues such as the skin, heart,
and uterus, where cells experience significant stretching or shearing
forces.
Desmosomes contribute to the overall integrity and strength of tissues,
helping them resist tearing or disruption during physical movements or
stresses. Here are detailed notes on desmosomes:

STRUCTURE OF DESMOSOMES:
Transmembrane Proteins: Desmosomes consist of transmembrane
proteins that extend across the plasma membrane of adjacent cells.
The primary transmembrane proteins found in desmosomes are
desmogleins and desmocollins.
Cadherin Family: Desmogleins and desmocollins belong to the
cadherin family of cell adhesion molecules. These cadherins interact
homophilically, meaning desmogleins on one cell bind to
desmogleins on an adjacent cell, and desmocollins on one cell bind
to desmocollins on an adjacent cell.

Desmosomal Plaque: Inside the cell, the cytoplasmic
tails of desmogleins and desmocollins are linked to
the desmosomal plaque, a dense region containing
various proteins. Plakoglobin and desmoplakin are
major proteins in the desmosomal plaque.
Intermediate Filaments: Desmoplakin connects the
desmosomal plaque to the intermediate filament
network within the cell. Intermediate filaments,
primarily composed of keratins, provide structural
support and anchor the desmosomes to the cell's
cytoskeleton.

FUNCTION OF DESMOSOMES
Mechanical Adhesion: The main
function of desmosomes is to provide
mechanical adhesion between cells. This
adhesion allows cells to resist mechanical
stress, such as stretching, compression, or
shear forces, within tissues. For example,
in the skin, desmosomes between
epidermal cells help maintain the overall
integrity and strength of the tissue.

Tissue Integrity: Desmosomes contribute to the
structural integrity of tissues, preventing the separation
of cells during physical movement or external forces.
Cell-to-Cell Communication: While desmosomes
primarily function as mechanical adhesion points, they
also play a role in cell-to-cell communication.

REGULATION AND PATHOLOGICAL
SIGNIFICANCE
Regulation: The formation and disassembly of
desmosomes are tightly regulated processes.
Various signalling pathways and protein interactions
control the assembly and stability of desmosomes.
For instance, calcium ions play a crucial role in
regulating the adhesive properties of cadherins.

REGULATION AND PATHOLOGICAL
SIGNIFICANCE
Pathological Significance: Mutations or dysregulation of
desmosomal proteins can lead to diseases known as
desmosomal cardiomyopathies and blistering skin
disorders. In desmosomal cardiomyopathies, the
mechanical integrity of cardiac tissue is compromised,
leading to heart dysfunction. In blistering skin disorders,
weakened desmosomal adhesion causes the epidermal
layers to separate, resulting in blister formation.

PLASMODESMATA
Plasmodesmata (singular: plasmodesma) are specialized
channels that facilitate communication and transport
between plant cells.
These microscopic structures create cytoplasmic connections,
allowing adjacent plant cells to share various molecules,
including water, ions, nutrients, and signalling molecules.
Plasmodesmata play a crucial role in coordinating growth,
development, and defense responses within plant tissues.

STRUCTURE OF PLASMODESMATA
Channels: Plasmodesmata are narrow channels that
traverse the cell walls of neighboring plant cells. They create
a direct cytoplasmic continuum between adjacent cells,
allowing for direct communication.
Plasma Membrane: The plasmodesmata are lined with the
plasma membrane, which encases the cytoplasmic sleeve
connecting two cells. The plasma membrane controls the
movement of molecules between cells through these channels.

STRUCTURE OF PLASMODESMATA
Cytoplasmic Sleeve: The cytoplasmic sleeve is the space
within the plasmodesmata that contains cytoplasm and cell
organelles. It provides a direct pathway for the movement of
substances between connected cells.
Desmotubule: In the center of the plasmodesma, there is a
strand-like structure called the desmotubule. The desmotubule
is a remnant of the endoplasmic reticulum (ER) that passes
through the plasmodesma and helps maintain its structure.

FUNCTION OF PLASMODESMATA
Intercellular Communication: Plasmodesmata allow plant
cells to communicate directly with each other.
This communication enables the coordinated response of
cells within a tissue to various developmental and
environmental signals.
Important signalling molecules, such as hormones and
defense-related molecules, can move through
plasmodesmata, propagating responses to neighboring cells.

Transport of Nutrients and Hormones:
Plasmodesmata facilitate the exchange of various
essential molecules, including nutrients (sugars, amino
acids), ions (e.g., potassium, calcium), and hormones
(e.g., auxins, cytokinins), between adjacent plant cells.
This transport is vital for supporting the growth and
development of plant tissues.

Cell-to-Cell Movement of Macromolecules:
Plasmodesmata also enable the movement of larger
macromolecules, such as proteins and nucleic acids,
between plant cells.
This feature plays a crucial role in coordinating plant
responses to infections and other stress conditions.

REGULATION OF PLASMODESMATA
Size Exclusion Limit: Plasmodesmata are regulated
by size exclusion limits.
The size of molecules that can pass through the
channels depends on the diameter of the
plasmodesmata and associated proteins. Smaller
molecules can pass more freely, while larger
molecules may require specific transport mechanisms.

Callose Deposition: The movement of molecules
through plasmodesmata can be controlled by the
deposition of callose, a polysaccharide.
Callose can temporarily block the channels,
restricting molecular exchange during certain
developmental or stress-related processes.

Plant Development and Environmental Cues:
Plasmodesmata regulation is influenced by plant
developmental signals and environmental cues.
Hormones and other signalling molecules can
modulate the permeability of plasmodesmata,
ensuring that specific responses occur in specific cells
or tissues.

SYNAPSES
Synapses are specialized junctions that enable communication
between neurons or between neurons and other cells in the
nervous system.
They are fundamental to the transmission of nerve impulses and
play a crucial role in various cognitive, sensory, and motor
functions.
Understanding the structure and function of synapses is
essential for comprehending how information is processed and
transmitted within the nervous system. :

STRUCTURE OF SYNAPSE
Presynaptic Terminal: The presynaptic terminal is the end of
the axon where neurotransmitters are released. When an action
potential reaches the presynaptic terminal, it triggers the
release of neurotransmitters into the synaptic cleft.
Synaptic Cleft: The synaptic cleft is a small fluid-filled gap that
separates the presynaptic terminal from the postsynaptic cell.
Neurotransmitters diffuse across this gap to transmit the signal
from the presynaptic neuron to the postsynaptic neuron.

STRUCTURE OF SYNAPSE
Postsynaptic Membrane: The postsynaptic membrane is the specialized
region on the receiving neuron where neurotransmitter receptors are
located. These receptors bind to neurotransmitters released by the
presynaptic neuron, initiating a response in the postsynaptic neuron.
Neurotransmitters: Neurotransmitters are chemical messengers that
carry signals across the synapse. They are stored in vesicles within the
presynaptic terminal and are released in response to an action
potential. The most common neurotransmitters include acetylcholine,
dopamine, serotonin, glutamate, and GABA (gamma-aminobutyric
acid).

TYPES OF SYNAPSES
Chemical Synapses: The majority of synapses in the
nervous system are chemical synapses.
In a chemical synapse, neurotransmitters are released
by the presynaptic neuron and bind to receptors on
the postsynaptic neuron, generating a response.
This type of synapse allows for signal amplification
and modulation.

TYPES OF SYNAPSES
Electrical Synapses: Electrical synapses, also known as gap
junctions, are less common but allow for direct electrical
communication between neurons.
In electrical synapses, connexin proteins form gap junction
channels that permit the direct flow of ions and small molecules
between adjacent cells, facilitating rapid and synchronized
transmission of signals.

GAP JUNCTIONS
Gap junctions are specialized cell-to-cell communication
channels found in various tissues throughout the body.
They facilitate direct communication and exchange of
ions, small molecules, and signalling molecules between
adjacent cells.
Gap junctions are crucial for coordinating cellular
activities and maintaining tissue homeostasis. Here are the
key features and functions of gap junctions:

STRUCTURE:
Gap junctions consist of connexons, which are formed
by hexameric assemblies of connexin proteins.
Connexins are transmembrane proteins that span the
cell membrane and create channels for communication.
Each connexon is made up of six connexin subunits,
and two connexons from adjacent cells align to form a
gap junction channel.

TIGHT JUNCTIONS
Tight junctions are specialized cell-to-cell junctions that
form a tight seal between adjacent cells in epithelial and
endothelial tissues.
Also known as occluding junctions or zonulae occludentes,
tight junctions play a critical role in regulating the passage
of molecules and ions between cells and creating a
selectively permeable barrier.

Structure: Tight junctions are cell junctions found
primarily in epithelial and endothelial tissues.
They create a seal or barrier between adjacent cells,
preventing the passage of substances between the cells.
Tight junctions consist of transmembrane proteins, such
as claudins and occludins, that interact with
complementary proteins on adjacent cells.

Function: Tight junctions play a crucial role in
maintaining the selective permeability of epithelial
and endothelial tissues.
By restricting the movement of molecules through
the intercellular space, tight junctions help regulate
the passage of ions, water, and solutes and
maintain tissue integrity.

Barrier Function:
The main function of tight junctions is to create a physical
barrier that separates the apical and basolateral domains
of epithelial and endothelial cells.
This barrier prevents the leakage of substances between
cells and allows for the establishment of concentration
gradients essential for various physiological processes.

Cell Polarity:
Tight junctions contribute to the establishment and
maintenance of cell polarity in epithelial cells.
They help maintain the distinct molecular
composition and functional differences between the
apical and basolateral surfaces of the cells.

Regulation:
The permeability of tight junctions can be
dynamically regulated in response to various
physiological and pathological cues.
Signalling pathways and environmental factors
can modulate tight junction proteins, influencing their
barrier properties.

Clinical Significance:
Dysfunction of tight junctions is implicated in
various diseases, including inflammatory bowel
diseases, leaky gut syndrome, and certain kidney
disorders.

COMPARISON BETWEEN GAP AND TIGHT
JUNCTIONS
Gap junctions and tight junctions are two different types
of cell junctions found in various tissues, and they serve
distinct functions. Here's a comparison between gap
junctions and tight junctions:

1. STRUCTURE:
Gap Junctions: Gap junctions are formed by connexons, which are
hexameric protein complexes made up of connexin proteins. These
connexons align between adjacent cells, creating channels that allow
the direct exchange of ions, small molecules, and signalling
molecules.
Tight Junctions: Tight junctions are composed of transmembrane
proteins, such as claudins and occludins, that interact with
complementary proteins on adjacent cells. Tight junctions create a
barrier between cells, sealing the intercellular space and preventing
the passage of substances between cells.

2. FUNCTION:
Gap Junctions: Gap junctions facilitate direct communication
between cells, allowing the passage of ions, small molecules, and
second messengers. This enables synchronized electrical and
chemical signalling between connected cells, contributing to
coordinated cellular responses.
Tight Junctions: Tight junctions create a physical barrier between
cells, regulating the passage of ions, water, and solutes across
epithelial and endothelial tissues. They maintain tissue integrity and
selectively control the movement of substances to establish
concentration gradients.

3. PERMEABILITY:
Gap Junctions: Gap junctions have high permeability,
allowing the direct exchange of ions and small molecules
between adjacent cells.
Tight Junctions: Tight junctions have low permeability,
restricting the movement of molecules through the
intercellular space. They establish a selective barrier to
control the passage of substances.

4. LOCATION:
Gap Junctions: Gap junctions are found in various
tissues, including cardiac muscle, smooth muscle,
neurons, and some epithelial tissues.
Tight Junctions: Tight junctions are primarily found
in epithelial and endothelial tissues, forming the
apical junctional complex that separates the apical
and basolateral domains of cells.

5. CELLULAR FUNCTION:
Gap Junctions: Gap junctions play a role in coordinating
electrical and chemical signals, contributing to functions like
cardiac rhythmicity, neural synchronization, and
coordinated smooth muscle contractions.
Tight Junctions: Tight junctions are crucial for maintaining
the barrier function of epithelial and endothelial tissues,
regulating nutrient absorption, waste elimination, and
protecting against pathogens.

6. REGULATION:
Gap Junctions: Gap junction permeability can be
regulated by various factors, such as calcium
concentration, pH, and phosphorylation status of
connexin proteins.
Tight Junctions: Tight junctions can be dynamically
regulated in response to physiological and
pathological cues, altering their barrier properties.

7. CLINICAL SIGNIFICANCE:
Gap Junctions: Dysfunction of gap junctions can lead
to various diseases, including cardiac arrhythmias,
neuropathies, and certain developmental disorders.
Tight Junctions: Tight junction dysfunction is
associated with conditions like inflammatory bowel
diseases, leaky gut syndrome, and certain kidney
disorders.

CELL-TO-CELL ADHESION: THE IMPORTANCE OF
CELL ADHESION IN MULTICELLULAR
ORGANISMS
Cell-to-cell adhesion is a critical process that enables cells to stick
together and form tissues and organs in multicellular organisms.
It plays a fundamental role in various physiological processes,
including development, tissue homeostasis, immune responses,
wound healing, and organ function.
The ability of cells to adhere to each other is essential for
maintaining the structural integrity of tissues and coordinating their
functions.

MECHANISMS OF CELL-TO-CELL ADHESION:
Cell-to-cell adhesion involves complex molecular
interactions between specific proteins and carbohydrates
on the surfaces of neighboring cells.
The process can be broadly categorized into two main
mechanisms: direct cell adhesion and indirect cell
adhesion.

MECHANISMS OF CELL-TO-CELL ADHESION:

DIRECT CELL ADHESION:
Cadherin Family: Cadherins are a major class of
transmembrane proteins responsible for direct cell adhesion.
They are calcium-dependent adhesion molecules that
mediate strong and specific homophilic interactions between
cells of the same type.
For example, E-cadherin promotes adhesion between
epithelial cells, while N-cadherin is involved in cell adhesion
in neural tissues.

https://www.researchgate.net/publication/47791127_Prowse_ABJ_Chong_F_Gray_PP_Munro_TP_Stem_cell_integ
rins_implications_for_ex-vivo_culture_and_cellular_therapies_Stem_Cell_Res_6_1-12/figures?lo=1&utm_source=go
ogle&utm_medium=organic

DIRECT CELL ADHESION:
Integrins: Integrins are another group of transmembrane
proteins that mediate cell adhesion, particularly in cell-
extracellular matrix interactions.
Integrins can bind to specific extracellular matrix proteins
like fibronectin and collagen, allowing cells to anchor to
the surrounding extracellular matrix and participate in
tissue organization.

https://www.youtube.com/watch?v=Ayz7kuEAQac

INTEGRIN STRUCTURE
Integrins are proteins that function mechanically, by attaching the cell
cytoskeleton to the extracellular matrix (ECM), and biochemically, by sensing
whether adhesion has occurred.
The integrin family of proteins consists of alpha and beta subtypes, which form
transmembrane heterodimers.
Integrins function as adhesion receptors for extracellular ligands and transduce
biochemical signals into the cell, through downstream effector proteins.
Remarkably, they function bidirectionally, meaning they can transmit
information both outside-in and inside-out

Integrin α subunit domains: Top: Linear domain arrangement. Middle: The globular
structure formed by protein domains. Bottom: simplified version of the integrin α
subunit. The αI domain is present in some subtypes of the α subunit.
EF-hand

Integrin subunit domains: Top: Linear domain arrangement. Middle: The globular structure formed
β
by protein domains. Bottom: simplified version of the integrin subunit.
β
EF-hand

INDIRECT CELL ADHESION:
Selectins: Selectins are a family of cell adhesion molecules
involved in cell interactions with carbohydrates on the surface of
other cells or the extracellular matrix. They mediate the initial
tethering and rolling of leukocytes during inflammatory
responses.
Immunoglobulin Superfamily: Immunoglobulin superfamily cell
adhesion molecules, such as ICAMs and VCAMs, play crucial roles
in immune cell adhesion and interactions between leukocytes and
endothelial cells during inflammation.

https://www.mdpi.com/2073-4409/10/3/577

TYPES OF CELL-TO-CELL ADHESION:
Cell-to-cell adhesion can occur in various forms, each tailored to
specific functions and contexts. Some of the prominent types of
cell adhesion include:
Desmosomes: Desmosomes are strong adhesion junctions found in
tissues subjected to mechanical stress, like skin and cardiac muscle.
They rely on cadherins, particularly desmogleins and
desmocollins, to connect the cytoskeletons of adjacent cells,
providing structural support and resistance to mechanical forces.

Adherens Junctions: Adherens junctions are cadherin-
based adhesion junctions that are crucial for
maintaining tissue integrity and cell polarity.
They form belts around epithelial cells, linking their
actin cytoskeletons and promoting cell cohesion.

Tight Junctions: Tight junctions create barriers between cells
in epithelial and endothelial tissues, regulating the passage
of ions and solutes. They are essential for establishing
selective permeability and maintaining tissue homeostasis.
Gap Junctions: Gap junctions enable direct communication
and molecular exchange between adjacent cells through
connexon channels. They play a role in coordinating
electrical and biochemical signals in excitable tissues.

Hemidesmosomes: Hemidesmosomes are specialized
adhesion structures that anchor epithelial cells to the
underlying basement membrane.
They involve integrins connecting to components of the
extracellular matrix.

BIOLOGICAL SIGNIFICANCE OF CELL-TO-
CELL ADHESION:
Cell-to-cell adhesion is vital for several biological processes and physiological
functions:
Tissue Formation: During embryonic development, cell adhesion is essential
for tissue formation and morphogenesis. The adhesion of cells allows them to
organize into specific tissues and structures, such as the formation of germ layers
during gastrulation.
Tissue Homeostasis: In adult organisms, cell-to-cell adhesion maintains tissue
integrity and prevents the disintegration of tissues. The presence of adherens
junctions, tight junctions, and desmosomes in epithelial tissues ensures their
structural integrity.

CELL ADHESION:
Immune Response: Cell adhesion molecules are critical for
immune responses. They facilitate leukocyte adhesion to the
endothelium during inflammation, enabling leukocytes to
migrate to sites of infection or injury.
Wound Healing: During wound healing, cell adhesion is
essential for the migration and proliferation of cells to repair
damaged tissues. Integrins and other adhesion molecules play
a crucial role in this process.

CELL ADHESION:
Cell Differentiation: Cell adhesion is involved in cell
differentiation and tissue specialization. For example, E-
cadherin is crucial for the differentiation of epithelial cells
during embryonic development.
Metastasis: In cancer, altered cell adhesion can contribute to
metastasis. Dysregulation of adhesion molecules can enable
cancer cells to detach from the primary tumor and invade other
tissues.

WHAT IS A CHEMICAL SIGNALLING
Chemical signalling is a form of communication that occurs between
cells, tissues, or organisms through the release and detection of
chemical substances.
These chemical signals, also known as signalling molecules or ligands,
can travel short or long distances to interact with specific receptors on
target cells.
The process of chemical signalling allows cells to coordinate their
activities, regulate physiological processes, and respond to changes in
their environment.

Chemical signalling is fundamental to various biological
processes in both unicellular and multicellular organisms. It
plays a crucial role in:
Cellular communication: Cells use chemical signals to relay
information to neighboring cells or distant target cells, enabling
them to respond to environmental cues or coordinate their
actions in complex multicellular organisms.

Cell-to-cell coordination: Within multicellular organisms,
chemical signalling helps different cell types work together
harmoniously to form tissues, organs, and systems.
Homeostasis: Chemical signalling is involved in maintaining the
internal balance and stability (homeostasis) of an organism by
regulating physiological processes like hormone release,
metabolic activity, and immune responses.

Development and growth: During embryonic development and tissue
regeneration, chemical signals guide the differentiation and growth
of cells into specific tissues and structures.
Immune responses: Immune cells use chemical signalling to
communicate and coordinate their actions, facilitating the recognition
and elimination of pathogens or abnormal cells.
Behavior and social interactions: In animals, chemical signals known
as pheromones play a crucial role in behaviors such as mating,
territorial marking, and group cohesion.

CHEMICAL SIGNALLING MECHANISMS CAN BE
BROADLY CATEGORIZED INTO TWO TYPES:
Endocrine signalling: In this form of signalling, cells release
hormones into the bloodstream. These hormones travel throughout
the body and affect distant target cells equipped with specific
receptors for that particular hormone.
Paracrine and Autocrine signalling: In paracrine signalling, cells
release chemical signals that act locally on nearby target cells.
Autocrine signalling is a special case of paracrine signalling, where
the cell releases signals that also act on its own receptors.

CHEMICAL SIGNALLING IN UNICELLULAR
ORGANISMS
Chemical signalling in unicellular organisms plays a vital role in
their survival, growth, and response to environmental changes.
These single-celled organisms have developed various mechanisms
to communicate with each other and their surroundings using
chemical signals.
Here are some common forms of chemical signalling in unicellular
organisms:

ORGANISMS
Quorum sensing: Quorum sensing is a prevalent form of chemical
signalling among unicellular organisms, particularly bacteria. It
involves the release and detection of small signalling molecules called
autoinducers. As the population of bacteria increases, the
concentration of autoinducers rises.
When the autoinducer concentration reaches a certain threshold
(quorum), it triggers specific responses in the bacterial community, such
as biofilm formation, virulence factor production, or cooperative
behavior.

ORGANISMS
Pheromones: Unicellular organisms, especially some algae
and protozoa, release pheromones to communicate with
individuals of the same species. Pheromones are chemical
substances that can evoke specific behaviors or physiological
responses in nearby cells or organisms. For example, certain
types of algae release pheromones to attract gametes during
sexual reproduction.

ORGANISMS
Chemotaxis: Chemotaxis is a movement response of unicellular organisms
to gradients of chemical substances in their environment. They can detect
and respond to varying concentrations of specific chemicals by either
moving towards or away from the source. This behavior allows them to seek
out beneficial environments or avoid harmful ones.
Response to environmental cues: Unicellular organisms can respond to
changes in their environment by altering their gene expression and
physiological functions. For instance, when exposed to stressors like heat,
toxins, or nutrient availability, they may activate specific genes that help
them adapt and survive.

ORGANISMS
Secondary metabolites: Some unicellular organisms produce and
release secondary metabolites, which are small molecules not
directly involved in growth or reproduction. These metabolites can
function as signalling molecules, influencing the behavior or
physiology of other organisms in the vicinity.
Horizontal gene transfer: Unicellular organisms can exchange
genetic material with their neighbors through processes like
conjugation, transduction, and transformation. These exchanges can
involve the transfer of genes responsible for signalling pathways,
thereby influencing the behavior of the recipient cell.

ROLE OF CELL SURFACE RECEPTORS IN
SIGNAL MEDIATION
Cell surface receptors play a crucial role in signal mediation, acting as
molecular intermediaries that facilitate communication between the
extracellular environment and the cell's interior.
They are responsible for detecting and binding specific signalling
molecules (ligands) and initiating intracellular signalling cascades, leading
to various cellular responses.

LIGAND BINDING:
The process begins when a signalling molecule, known as the ligand,
encounters and binds to the extracellular domain of its specific cell
surface receptor.
The binding event is highly specific, like a lock-and-key mechanism,
ensuring that only the appropriate ligand can activate the
corresponding receptor.

RECEPTOR ACTIVATION:
Ligand binding induces conformational changes in the
receptor, triggering its activation.
This activation can involve dimerization (receptor pairs
coming together) or conformational shifts that expose or
hide specific regions on the receptor's cytoplasmic side.

INITIATION OF INTRACELLULAR SIGNALLING:
Once activated, the cell surface receptor acts as a molecular
switch, initiating intracellular signalling pathways.
Different types of cell surface receptors activate distinct
downstream signalling pathways that lead to diverse cellular
responses.

ACTIVATION OF SECOND MESSENGER SYSTEMS:
 Some receptors, like G protein-coupled receptors (GPCRs), activate
intracellular second messenger systems.
 Upon activation, GPCRs interact with intracellular G proteins, leading to the
production of second messengers such as cyclic AMP (cAMP) or inositol
trisphosphate (IP3).
 Second messengers amplify the original signal, propagating it further within
the cell.

KINASE CASCADES:
Other receptors, such as receptor tyrosine kinases (RTKs), possess
intrinsic kinase activity.
Ligand binding to RTKs leads to receptor dimerization and
autophosphorylation of specific tyrosine residues in the receptor's
cytoplasmic domain.
These phosphorylated tyrosines serve as docking sites for
downstream signalling proteins, initiating kinase cascades that
transmit the signal.

GENE EXPRESSION CHANGES:
Many signalling pathways activated by cell surface receptors
ultimately lead to changes in gene expression.
Transcription factors are often involved, controlling the expression
of specific genes in response to the signal received by the
receptor.

CELLULAR RESPONSE:
The culmination of the intracellular signalling events is a cellular
response, which can vary widely depending on the specific
receptor and downstream pathways involved.
Cellular responses may include changes in metabolism,
proliferation, differentiation, secretion, cell movement, or
apoptosis.

SIGNAL TERMINATION AND REGULATION:
To maintain cellular homeostasis, signal termination mechanisms
come into play.
Receptor internalization through endocytosis can remove the
activated receptors from the cell surface, attenuating the signal.
Negative feedback loops and other regulatory mechanisms ensure
that the cellular response is appropriately controlled.

INTRACELLULAR RECEPTORS:
Introduction to Intracellular Receptors:
Intracellular receptors are a class of receptors located
inside the cell, typically in the cytoplasm or nucleus.
They are distinct from cell surface receptors, which are
located on the cell membrane.

Ligand Types:
 Intracellular receptors primarily bind to hydrophobic ligands, such as
steroid hormones (e.g., estrogen, testosterone) and thyroid hormones.
 These ligands can diffuse through the cell membrane due to their
lipid solubility.

Mechanism of Activation:
When a hydrophobic ligand enters the cell and binds to
the intracellular receptor, it induces a conformational
change, activating the receptor.
Nuclear Localization:
Activated intracellular receptors can translocate to the
nucleus, where they act as transcription factors.

Gene Expression Regulation:
 In the nucleus, intracellular receptors directly bind to specific DNA sequences called hormone response
elements (HREs) on target genes.
 Binding of the receptor to the HREs influences gene transcription, leading to changes in protein synthesis.
Cellular Response:
 By regulating gene expression, intracellular receptors control various cellular processes, such as growth,
development, and metabolism.

Example of Action:
 The activation of estrogen receptors by estrogen hormone leads to gene expression changes that influence
female reproductive processes.
Physiological Importance:
 Intracellular receptors play a critical role in mediating the effects of steroid hormones and other
hydrophobic ligands.
 They contribute to maintaining homeostasis and coordinating the response to changing internal
environments.
Pharmaceutical Significance:
 Intracellular receptors are important targets for pharmacological interventions.
 Hormone-based therapies, such as estrogen replacement therapy, target intracellular receptors to treat
hormonal imbalances.

ROLE OF INTRACELLULAR RECEPTORS IN
SIGNAL MEDIATION
The role of intracellular receptors in signal mediation is to translate
specific signals carried by hydrophobic ligands into changes in gene
expression, which ultimately leads to various cellular responses.
These receptors are located inside the cell, typically in the cytoplasm or
nucleus, and primarily interact with lipophilic (hydrophobic) signalling
molecules, such as steroid hormones and thyroid hormones.

ROLE OF INTRACELLULAR RECEPTORS IN
SIGNAL MEDIATION
Ligand Binding and Activation:
Nuclear Translocation:
DNA Binding and Gene Regulation:
Gene Expression Changes:
Cellular Responses:
Physiological Significance

IMPORTANCE OF
SECOND MESSENGERS IN SIGNAL TRANSDUCTION
cAMP,
cGMP,
calcium ions,
phosphatidyl inositol,
phytohormones.

IMPORTANCE OF cAMP IN SIGNAL
TRANSDUCTION
Amplification of Signals:
cAMP acts as a potent signal amplifier. When an extracellular ligand
binds to a G protein-coupled receptor (GPCR), it activates a G protein
that stimulates adenylyl cyclase to produce cAMP.
Each activated adenylyl cyclase can generate many cAMP molecules,
leading to a significant amplification of the initial signal.
This amplification step ensures that even small changes in the
extracellular environment can trigger robust cellular responses.

TRANSDUCTION
Activation of Protein Kinase A (PKA):
cAMP activates the intracellular enzyme protein kinase A
(PKA).
PKA is a serine/threonine kinase that phosphorylates specific
target proteins in response to elevated cAMP levels.
Phosphorylation by PKA alters the activity of target proteins,
leading to diverse cellular responses.

TRANSDUCTION
Regulation of Metabolism:
cAMP-PKA signalling regulates various metabolic processes,
such as glycogen breakdown and glucose metabolism.
In response to signals like adrenaline, cAMP-PKA activation
stimulates glycogen breakdown into glucose, providing energy
for the "fight or flight" response.

TRANSDUCTION
Control of Cellular Proliferation:
cAMP-PKA signalling influences cell growth and
proliferation by modulating gene expression and cell
cycle regulators.
Dysregulation of cAMP signalling pathways is
associated with several diseases, including cancer.

TRANSDUCTION
Neurotransmission and Neuronal Plasticity:
In neurons, cAMP plays a role in neurotransmission and
synaptic plasticity.
It modulates the activity of ion channels and neurotransmitter
receptors, affecting synaptic strength and information
processing in the brain.

TRANSDUCTION
Regulation of Ion Channels:
cAMP-PKA signalling can modulate the activity of various ion
channels, influencing cellular excitability and electrical
signalling.
For example, in the heart, cAMP increases the activity of
calcium channels, leading to enhanced contractility and heart
rate.

TRANSDUCTION
Immune Response Modulation:
cAMP-PKA signalling is involved in regulating immune
responses.
It can inhibit the activation of certain immune cells,
dampening inflammation and immune reactions.

TRANSDUCTION
Therapeutic Targets:
The importance of cAMP in cellular processes makes it
an attractive target for drug development.
Drugs that affect cAMP levels or PKA activity have
therapeutic potential in various diseases, such as heart
failure, asthma, and mental disorders.

IMPORTANCE OF cGMP IN SIGNAL
TRANSDUCTION
Activation of Protein Kinase G (PKG):
Similar to cAMP and protein kinase A (PKA), cGMP activates
protein kinase G (PKG), also known as cGMP-dependent
protein kinase.
PKG is a serine/threonine kinase that phosphorylates
specific target proteins in response to elevated cGMP levels.
Phosphorylation by PKG modulates the activity of these
target proteins, leading to diverse cellular responses.

TRANSDUCTION
Regulation of Smooth Muscle Relaxation:
One of the most well-known roles of cGMP is in smooth
muscle relaxation.
In vascular smooth muscle cells, cGMP-PKG signalling is
stimulated by nitric oxide (NO), leading to vasodilation and
improved blood flow.
Similarly, in the gastrointestinal tract, cGMP signalling
mediates relaxation of smooth muscle, facilitating digestion.

TRANSDUCTION
Vision and Phototransduction:
In photoreceptor cells of the retina, cGMP is involved in
the process of vision and phototransduction.
Light causes the activation of rhodopsin, leading to a
decrease in cGMP levels, which closes cGMP-gated ion
channels in the photoreceptor cells.
This closure of ion channels hyperpolarizes the cell,
initiating the neural signal for vision.

TRANSDUCTION
Regulation of Ion Channels:
cGMP-PKG signalling can modulate the activity
of certain ion channels in various cell types.
For example, in cardiac myocytes, cGMP can
enhance the activity of potassium channels,
leading to cardiac relaxation.

TRANSDUCTION
Neurotransmission and Synaptic Plasticity:
In the nervous system, cGMP is involved in
neurotransmission and synaptic plasticity.
It can modulate synaptic strength and influence the
release of neurotransmitters.

TRANSDUCTION
Regulation of Cell Growth and Proliferation:
cGMP signalling can impact cell growth and proliferation
by regulating gene expression and cell cycle control.
It has been implicated in processes like cell differentiation
and wound healing.

TRANSDUCTION
Phototransduction in Plants:
In plants, cGMP is involved in phototransduction
and the response to light.
It regulates processes like stomatal opening and
chloroplast movement.

TRANSDUCTION
Therapeutic Relevance:
Dysregulation of cGMP signalling is associated with
various diseases, including cardiovascular
disorders, pulmonary hypertension, and erectile
dysfunction.
Drugs targeting cGMP signalling pathways are
used for treating some of these conditions.

IMPORTANCE OF CALCIUM IONS IN SIGNAL
TRANSDUCTION
Ubiquitous Second Messengers:
Calcium ions act as second messengers in response to a
wide range of extracellular signals, including
neurotransmitters, hormones, and mechanical stimuli.
Their versatility allows cells to respond to diverse
signalling inputs and coordinate various physiological
responses.

TRANSDUCTION
Intracellular Calcium Concentration Regulation:
Calcium signalling involves tightly regulated changes in
intracellular calcium concentration ([Ca2
+
])i.
Normally, resting [Ca2
+
]i is kept low by active pumping of
calcium out of the cell or into intracellular compartments.
Upon stimulation, specific signalling pathways increase
[Ca2
+
]i, leading to transient or sustained calcium signals.

TRANSDUCTION
Activation of Calmodulin and Protein Kinases:
Increased [Ca2+]i leads to the binding of calcium ions to
calmodulin, a calcium-binding protein.
The calcium-calmodulin complex can activate various
enzymes, including protein kinases, such as calmodulin-
dependent protein kinases (CaMKs).
CaMKs then phosphorylate specific target proteins,
modulating their activity and influencing cellular responses.

TRANSDUCTION
Muscle Contraction:
In muscle cells, calcium ions play a crucial role in
excitation-contraction coupling.
During muscle activation, an action potential
triggers the release of calcium ions from the
sarcoplasmic reticulum, which initiates muscle
contraction.

TRANSDUCTION
Neurotransmitter Release:
In neurons, calcium signalling is essential for
neurotransmitter release at synapses.
The influx of calcium ions into the presynaptic
terminal triggers vesicle fusion and the release of
neurotransmitters into the synaptic cleft.

TRANSDUCTION
Cell Migration and Cytoskeletal Dynamics:
Calcium signalling is involved in cell migration and
cytoskeletal dynamics.
Calcium ions can regulate actin and myosin
filaments, influencing cell shape changes and
movement.

TRANSDUCTION
Gene Expression Regulation:
Calcium signalling can modulate gene expression by
activating specific transcription factors.
Transcription factors activated by calcium may regulate
the expression of genes involved in various cellular
processes, including development and immune responses.

TRANSDUCTION
Immune Response Modulation:
Calcium signalling plays a role in immune
responses, including activation of T cells and the
release of cytokines.
Calcium signals are crucial for the proper
functioning of immune cells.

TRANSDUCTION
Cell Death and Apoptosis:
Aberrant calcium signalling can lead to cell death
through apoptosis.
Dysregulation of calcium homeostasis has been
linked to neurodegenerative diseases and other
pathological conditions.

TRANSDUCTION
Calcium signalling pathways are potential targets for
drug development.
Calcium channel blockers, for instance, are used to treat
hypertension and heart-related conditions by modulating
calcium entry into cells.

IMPORTANCE OF PHOSPHATIDYL INOSITOL
IN SIGNAL TRANSDUCTION
Phosphoinositide Signalling Network:
Phosphatidylinositol is a phospholipid present in the cell
membrane, serving as a precursor for several
phosphorylated derivatives, collectively known as
phosphoinositides.
Phosphoinositides form a dynamic signalling network that
regulates numerous cellular processes, including cell
growth, differentiation, migration, and survival.

Phospholipid Kinases and Phosphatases:
The levels of phosphoinositides are tightly regulated by
the action of specific kinases and phosphatases.
Phospholipid kinases add phosphate groups to
phosphatidylinositol, generating different
phosphoinositides with distinct cellular functions.
Phospholipid phosphatases remove phosphate groups,
reversing the signalling events.

Phosphoinositide Binding Proteins:
Phosphoinositides act as docking sites for various proteins
containing specific domains, such as pleckstrin homology
(PH) domains or FYVE domains.
These phosphoinositide-binding proteins serve as
effectors, recruiting and regulating signalling proteins at
specific cellular locations.

Formation of Second Messengers:
Upon activation of cell surface receptors,
phosphoinositides are rapidly phosphorylated to
generate second messengers, such as inositol 1,4,5-
trisphosphate (IP3) and diacylglycerol (DAG).
IP3 triggers calcium release from intracellular stores, while
DAG activates protein kinase C (PKC), both contributing
to downstream signalling events.

Regulation of Protein Kinases and Signalling
Cascades:
Phosphoinositides regulate the activity of several protein
kinases, including PKC, Akt (protein kinase B), and PIP3-
dependent kinase-1 (PDK1).
These kinases are involved in crucial cellular processes,
including cell survival, metabolism, and proliferation.

Actin Cytoskeleton Dynamics:
Phosphoinositides influence actin cytoskeleton dynamics
and cell motility through interactions with actin-binding
proteins.
They contribute to processes like cell migration, shape
changes, and membrane remodeling.

Endocytosis and Membrane Trafficking:
Phosphoinositides play a role in endocytosis and vesicle
trafficking, regulating membrane fusion, and
internalization of cell surface receptors.
They are essential for the dynamic organization of
membrane compartments within the cell.

Neuronal Signalling:
In neurons, phosphoinositides are involved in synaptic
vesicle exocytosis and recycling, regulating
neurotransmitter release and synaptic plasticity.

Pathological Implications:
Dysregulation of phosphoinositide signalling is
associated with various diseases, including cancer,
neurodegenerative disorders, and immune
dysfunctions.

Components of the phosphoinositide signalling pathway are potential
targets for drug development.
Modulating phosphoinositide levels or targeting specific
phosphoinositide-binding proteins may have therapeutic benefits in
certain diseases including cancer, viral infection, neurodegenerative
diseases, developmental disorders, diabetes and inflammatory
diseases.

IMPORTANCE OF PHYTOHORMONES IN
SIGNAL TRANSDUCTION
Coordination of Plant Growth and Development:
Phytohormones regulate plant growth and development by
influencing cell division, elongation, and differentiation.
They control processes like seed germination, root and shoot
growth, leaf senescence, and flowering.

SIGNAL TRANSDUCTION
Response to Environmental Stimuli:
Phytohormones enable plants to respond to various environmental
cues, such as light, gravity, temperature, and stress factors.
They modulate adaptive responses, such as phototropism,
gravitropism, and responses to biotic and abiotic stresses.

SIGNAL TRANSDUCTION
Seed Development and Dormancy:
Phytohormones are involved in seed development,
dormancy, and germination.
They regulate the transition of seeds from dormancy to active
growth in response to favorable environmental conditions.

SIGNAL TRANSDUCTION
Flowering and Reproduction:
Phytohormones control flowering processes, including the
initiation and development of flowers.
They also influence the formation and ripening of fruits.

SIGNAL TRANSDUCTION
Leaf Senescence and Abscission:
Phytohormones regulate leaf senescence, the natural process of
aging and deterioration in leaves.
They also play a role in leaf abscission, the shedding of leaves
in response to changing environmental conditions.

SIGNAL TRANSDUCTION
Signal Transduction Pathways:
Phytohormones activate intracellular signalling pathways that
mediate their effects on gene expression and cellular responses.
These pathways involve receptor proteins, kinases, and
transcription factors.

SIGNAL TRANSDUCTION
Interactions and Crosstalk:
Phytohormones often interact with each other and engage in
crosstalk, leading to complex and integrated responses.
This interplay allows plants to fine-tune their responses to
changing environmental conditions.

SIGNAL TRANSDUCTION
Role in Plant Defense and Immunity:
Some phytohormones, like salicylic acid and jasmonic acid, are involved
in plant defense responses against pathogens and pests.
They trigger the expression of defense-related genes and the production
of antimicrobial compounds.

SIGNAL TRANSDUCTION
Role in Symbiotic Relationships:
Phytohormones play a role in establishing and maintaining
symbiotic relationships between plants and beneficial
microorganisms, such as mycorrhizal fungi and nitrogen-fixing
bacteria.

SIGNAL TRANSDUCTION
Agricultural and Horticultural Applications:
Understanding phytohormone signalling has significant
implications in agriculture and horticulture.
Manipulating phytohormone levels or responses can lead to
improved crop yields, disease resistance, and stress tolerance.

Unit 5- Cell Interactions and Signal Transduction.ppt

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Unit 5- Cell Interactions and Signal Transduction.ppt