Cell signalling
- 2. • Introduction • Extracellular signaling • Classification of cell signaling • Signal transduction & Types • Receptors & Types • Intracellular signaling • Secondary Messengers & Classification • Discussion • Conclusion • Reference
- 3. • Cell signaling is the process of cells communicating with other cells within the body, or with the external environment. As a process, cell signaling refers to a vast network of communication between, and within, each cell of our body. • Cell Signaling is part of biological communication process that governs basic activities of cells and coordinates multiple- cell actions.
- 4. • The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis. • Errors in singnaling intractions and cellular information processing may cause such as cancer, autoimmunity, and diabetes.
- 5. • Extracellular signalling molecules are cues, such as growth factors, hormones, cytokines, extracellular matrix components and neurotransmitters, designed to transmit specific information to target cells. • Signaling by extracellular, secreted molecules can be classified into four types. • Paracrine Synaptic signaling • Autocrine • Endocrine • Signaling by direct contact
- 6. • The signaling molecules released by one cell act on neighboring target cells (neurotransmitters).This type of signaling, in which cells communicate over relatively short distances, is known as paracrine signaling.
- 7. • One unique example of paracrine signaling is synaptic signaling, in which nerve cells transmits signals. • This process is named for the synapse, the junction between two nerve cells where signal transmission occurs.
- 8. • In autocrine signaling, a cell signals to itself, releasing a ligand that binds to receptors on its own surface. • Autocrine signaling is important in cancer and is thought to play a key role in metastasis
- 9. • Endocrine signaling, signals are produced by specialized cells and released into the bloodstream, which carries them to target cells in distant parts of the body. • Signals that are produced in one part of the body and travel through the circulation to reach far-away targets are known as Endocrine (hormones).
- 10. • Gap junctions in animals and plasmodesmata in plants are tiny channels that directly connect neighboring cells. • These water-filled channels allow small signaling molecules, called intracellular mediators, to travels between the two cells. • Small molecules, such as calcium ions ( Ca2+ )are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels without special assistance.
- 11. • Signal transduction is the transmission of molecular signals from a cell's exterior to its interior. Signals received by cells must be transmitted effectively into the cell to ensure an appropriate response. This step is initiated by cell-surface receptors. • There are three types:- Reception Transduction Response
- 12. • Reception: A cell detects a signaling molecule from outside of the cell. A signal is detected when the chemical signal (also known as a ligand) binds to a receptor protein on the surface of the cell or inside the cell. • Transduction: When the signaling molecule binds the receptor it changes the receptor protein in some way. This change initiates the process of transduction. Signal transduction is usually a pathway of several steps. Each relay molecule in the signal transduction pathway changes the next molecule in the pathway. • Response: Finally, the signal triggers a specific cellular response.
- 14. • Receptors are protein molecules inside the target cell or on its surface that receive a chemical signal. • There are two basic types of receptors: 1.Internal receptors 2.Cell surface receptors
- 15. • Internal receptors are found in the cytoplasm of the cell and respond to ligands that cross the cell membrane into the cell. These receptors can have a direct effect on protein production by binding directly to the DNA. • Example:- Steroid hormones.
- 16. • Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored, or integral proteins that bind to external ligand molecules. • This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. • Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The size and extent of each of these domains vary widely, depending on the type of receptor.
- 17. • There are three general categories of cell-surface receptors: • Ion channel-linked receptors • G-protein-linked receptors • Enzyme-coupled receptors.
- 18. • Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. To form a channel. • When a ligand binds to the extracellular region of the channel, there is a conformational change in the proteins structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through. • Example. Glucose
- 19. • G-protein-coupled receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane. • These transmembrane receptors play a key role in the processing of odours and the recognition of hormones.
- 20. • When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type.
- 21. • Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. • In some cases, the intracellular domain of the receptor itself is an enzyme. • When a ligand binds to the extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response.
- 23. • Intracellular signaling is an important mechanism by which cells can respond to their environment and extracellular cues. Cells can sense their environment and modify gene expression, mRNA splicing, protein expression and protein modifications in order to respond to these extracellular cues.
- 24. • Secondary messengers are intracellular signaling molecules realeased by the cell to trigger physiological changes such as proliferation, differentiation, migration, servival, and apoptosis. • second messengers and there one of the initiating components of intracellular signal transduction cascades. • Example of secondary messengers include cycle AMP, cyclic GMP, Inositol triphosphate, Diacylglycerol and Calcium.
- 25. Hydrophobic Molecules:-membrane- associated e.g. Hydrophilic molecules:- water souble molecules, such as , , and , located within the cytosol. Gases:- , and which can diffuse both through cytosol and across cellular membranes.
- 26. • Cyclic adenosine monophosphate (cAMP, cyclic AMP) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms.
- 27. • cAMP-PKA signaling pathway plays an important role in many biological processes including glycogen metabolism. • First, cyclic AMP is Formed from ATP by the the action of and degraded to AMP by . • The adrenaline/ glucagon receptor is coupled to adenylyl cyclase via G protein that simulate enzymes activity, thereby increasing the intracellular concentration of cAMP. • The inactive form of protein kinase A is tetramer consisting of two catalytic and two regulatory subunits.
- 28. • Cyclic AMP binds to the regulatory subunits are then enzymatically active and able to phosphorylate serine residues on their target proteins. • In the regulation of glycogen metabolism, protein kinase A phosphorylates two key target enzymes. • The first is another protein kinase, phosphorylase kinase,which is phosphorylated and activated by protein kinase A. • Phosphorylase kinase in turn phosphoraylates and activates glycogen phosphorylase, which catalyzes the breakdown of glycogen to glucose-1-phosphates.
- 30. • In addition, protein kinase A phosphorylates the enzyme glycogen synthase,which catalyzes glycogen synthesis. In this case phosphorylation inhibits enzymatic activity. • Elevation of cAMP and activation of protein kinase A thus block futher glycogen synthesis at the same time as it simulates glycogen breakdown. • Each molecules of adrenaline activates only a single receptor, each receptor may activate up to hundred molecules of Gs. Each Gs molecules the stimulates the enzymatic activities of adenylyl cyclase, which can catalyze the synthesis of many molecules of cAMP. • In many animal cells, increases in cAMP activate the transcription of specific target genes that contain a regulatory sequence called the cAMP response element or CRE.
- 31. • In this case, the signal carried out from the cytoplasm to the nucleus by the catalytic subunit of protein kinase A, which able to enter the nucleus following its release from the regulatory subunit. • Within the nucleus, Protein kinase A phosphorylates a transcription factor called CREB, leading to the activation of cAMP-inducible genes. • Such regulation of gene expression by cAMP plays important roles in controlling the proliferation, servival, and differentiation of a wide variety of animal cells.
- 32. • Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane- impermeable peptide hormones to the external cell surface. Its roles are not as clearly understood.
- 33. • One well-characterized role of cGMP is in the vertebrate eye,where it serves as the second messenger responsible for converting the visual signals received as light to nerve impulses. • The photoreceptor in rod cells of the retina is a G-protein couple receptor called rhodopsin. • Rhodopsin is activated as a result of the absorption of light by the associated small molecule 11-cis-retinal, which then isomerizes to all- trans-retinal inducing a conformational change in the rhodopsin protein. • Rhodopsin then activates the G protein transduction and the α subunit of transduction stimulates the activity of cGMP phoshodiesterase leading a decrease in the intracellular levels of cGMP.
- 34. • The change in cGMP level in retinal rod/ cone cells is translated to a nerve impulse by a direct effect of cGMP on ion channels in the plasma membrane, similar to the action of cAMP in sensing smells.
- 35. • The negatively charged phospholipid, phosphatidylinositol bisphosphate (PIP2), is present in the plasma membrane. A variety of hormones and growth factors stimulate the hydrolysis of PIP2 by phospholipase C to produce the two distinct second messengers, inositol1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
- 36. • Calcium ions are one type of second messengers and are responsible for many important physiological functions including muscle contraction, fertilization and neurotransmitter release. • IP3 quickly travels through the cytosol and binds to an IP3-gated calcium channel in the ER membrane , causing it to open. • Calcium ion flow out of the ER, raising the Ca2+ levels in the cytosol. • Diacylglycerol and Ca2+ activate protein kinase C at the surface of the plasma membrane. • Phosphorylation of cellular proteins by protein kinase C produces some of the cell responses to the hormone.
- 38. Cell typically receive signals in chemical from via various signaling molecules. When a signal molecules joins appropriate receptor on a cell surface, this triggers a chain of events that not only carries the signal to the cell interior, but amplifies it as well.
- 39. • Khan Academy • Wikipedia • Internet URL