![Figure 11.13
Mitochondrion
EXTRACELLULAR
FLUID
Plasma
membrane
Ca2
pump
Nucleus
CYTOSOL
Ca2
pump
Ca2
pump
Endoplasmic
reticulum
(ER)
ATP
ATP
Low [Ca2
]
High [Ca2
]
Key](https://image.slidesharecdn.com/cellcellinteraction-240917134022-1a8add2e/85/molecular-mechanism-of-cell-cell-interaction-ppt-45-320.jpg)
molecular mechanism of cell cell interaction.ppt
- 1. Cell to Cell Interactions
- 2. Overview: Cellular Messaging • Cell-to-cell communication is essential for both multicellular and unicellular organisms • Biologists have discovered some universal mechanisms of cellular regulation • Cells most often communicate with each other via chemical signals • For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine © 2011 Pearson Education, Inc.
- 3. Figure 11.1
- 4. External signals are converted to responses within the cell • Microbes provide a glimpse of the role of cell signaling in the evolution of life © 2011 Pearson Education, Inc.
- 5. Evolution of Cell Signaling • The yeast, Saccharomyces cerevisiae, has two mating types, a and • Cells of different mating types locate each other via secreted factors specific to each type • A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response • Signal transduction pathways convert signals on a cell’s surface into cellular responses © 2011 Pearson Education, Inc.
- 6. Figure 1 Exchange of mating factors Receptor factor a factor Yeast cell, mating type a Yeast cell, mating type Mating New a/ cell 1 2 3 a a a/
- 7. • Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes • The concentration of signaling molecules allows bacteria to sense local population density © 2011 Pearson Education, Inc.
- 8. Individual rod-shaped cells Spore-forming structure (fruiting body) Aggregation in progress Fruiting bodies 1 2 3 0.5 mm 2.5 mm Figure 11.3
- 9. Local and Long-Distance Signaling • Cells in a multicellular organism communicate by chemical messengers • Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells • In local signaling, animal cells may communicate by direct contact, or cell-cell recognition © 2011 Pearson Education, Inc.
- 10. Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions (b) Cell-cell recognition
- 11. • In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances • In long-distance signaling, plants and animals use chemicals called hormones • The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal © 2011 Pearson Education, Inc.
- 12. Figure 11.5a Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid. (a) Paracrine signaling (b) Synaptic signaling Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Target cell is stimulated.
- 13. Figure 11.5b Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling
- 14. The Three Stages of Cell Signaling: A Preview • Earl W. Sutherland discovered how the hormone epinephrine acts on cells • Sutherland suggested that cells receiving signals went through three processes – Reception – Transduction – Response © 2011 Pearson Education, Inc.
- 15. © 2011 Pearson Education, Inc. Animation: Overview of Cell Signaling Right-click slide / select “Play”
- 16. Figure 11.6-1 Plasma membrane EXTRACELLULAR FLUID CYTOPLASM Reception Receptor Signaling molecule 1
- 17. Figure 11.6-2 Plasma membrane EXTRACELLULAR FLUID CYTOPLASM Reception Transduction Receptor Signaling molecule Relay molecules in a signal transduction pathway 2 1
- 18. Figure 11.6-3 Plasma membrane EXTRACELLULAR FLUID CYTOPLASM Reception Transduction Response Receptor Signaling molecule Activation of cellular response Relay molecules in a signal transduction pathway 3 2 1
- 19. Reception: A signaling molecule binds to a receptor protein, causing it to change shape • The binding between a signal molecule (ligand) and receptor is highly specific • A shape change in a receptor is often the initial transduction of the signal • Most signal receptors are plasma membrane proteins © 2011 Pearson Education, Inc.
- 20. Receptors in the Plasma Membrane • Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane • There are three main types of membrane receptors – G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors © 2011 Pearson Education, Inc.
- 21. • G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors • A GPCR is a plasma membrane receptor that works with the help of a G protein • The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive © 2011 Pearson Education, Inc.
- 22. Figure 11.7a G protein-coupled receptor Signaling molecule binding site Segment that interacts with G proteins
- 23. Figure 11.7b G protein-coupled receptor 2 1 3 4 Plasma membrane G protein (inactive) CYTOPLASM Enzyme Activated receptor Signaling molecule Inactive enzyme Activated enzyme Cellular response GDP GTP GDP GTP GTP P i GDP GDP
- 24. • Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once • Abnormal functioning of RTKs is associated with many types of cancers © 2011 Pearson Education, Inc.
- 25. Figure 11.7c Signaling molecule (ligand) 2 1 3 4 Ligand-binding site helix in the membrane Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Signaling molecule Dimer Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr P P P P P P P P P P P P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Activated relay proteins Cellular response 1 Cellular response 2 Inactive relay proteins 6 ATP 6 ADP
- 26. • A ligand-gated ion channel receptor acts as a gate when the receptor changes shape • When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+ , through a channel in the receptor © 2011 Pearson Education, Inc.
- 27. Figure 11.7d Signaling molecule (ligand) 2 1 3 Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed
- 28. Intracellular Receptors • Intracellular receptor proteins are found in the cytosol or nucleus of target cells • Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors • Examples of hydrophobic messengers are the steroid and thyroid hormones of animals • An activated hormone-receptor complex can act as a transcription factor, turning on specific genes © 2011 Pearson Education, Inc.
- 34. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Signal transduction usually involves multiple steps • Multistep pathways can amplify a signal: A few molecules can produce a large cellular response • Multistep pathways provide more opportunities for coordination and regulation of the cellular response © 2011 Pearson Education, Inc.
- 35. Signal Transduction Pathways • The molecules that relay a signal from receptor to response are mostly proteins • Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated • At each step, the signal is transduced into a different form, usually a shape change in a protein © 2011 Pearson Education, Inc.
- 36. Protein Phosphorylation and Dephosphorylation • In many pathways, the signal is transmitted by a cascade of protein phosphorylations • Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation © 2011 Pearson Education, Inc.
- 37. • Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation • This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required © 2011 Pearson Education, Inc.
- 38. Receptor Signaling molecule Activated relay molecule P h o s p h o r y l a t i o n c a s c a d e Inactive protein kinase 1 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein Cellular response ATP ADP ATP ADP ATP ADP PP PP PP P P P P i P i P i Figure 11.10
- 39. Small Molecules and Ions as Second Messengers • The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger” • Second messengers are small, nonprotein, water- soluble molecules or ions that spread throughout a cell by diffusion • Second messengers participate in pathways initiated by GPCRs and RTKs • Cyclic AMP and calcium ions are common second messengers © 2011 Pearson Education, Inc.
- 40. Cyclic AMP • Cyclic AMP (cAMP) is one of the most widely used second messengers • Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal © 2011 Pearson Education, Inc.
- 41. Figure 11.11 Adenylyl cyclase Phosphodiesterase Pyrophosphate AMP H2O ATP P i P cAMP
- 42. • Many signal molecules trigger formation of cAMP • Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases • cAMP usually activates protein kinase A, which phosphorylates various other proteins • Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase © 2011 Pearson Education, Inc.
- 43. Figure 11.12 G protein First messenger (signaling molecule such as epinephrine) G protein-coupled receptor Adenylyl cyclase Second messenger Cellular responses Protein kinase A GTP ATP cAMP
- 44. Calcium Ions and Inositol Triphosphate (IP3) • Calcium ions (Ca2+ ) act as a second messenger in many pathways • Calcium is an important second messenger because cells can regulate its concentration © 2011 Pearson Education, Inc.
- 46. • A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol • Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers © 2011 Pearson Education, Inc.
- 47. © 2011 Pearson Education, Inc. Animation: Signal Transduction Pathways Right-click slide / select “Play”
- 48. G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca2 GTP Figure 11.14-1
- 49. Figure 11.14-2 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca2 (second messenger) Ca2 GTP
- 50. Figure 11.14-3 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Cellular responses Ca2 (second messenger) Ca2 GTP
- 51. Response: Cell signaling leads to regulation of transcription or cytoplasmic activities • The cell’s response to an extracellular signal is sometimes called the “output response” © 2011 Pearson Education, Inc.
- 52. Nuclear and Cytoplasmic Responses • Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities • The response may occur in the cytoplasm or in the nucleus • Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus • The final activated molecule in the signaling pathway may function as a transcription factor © 2011 Pearson Education, Inc.
- 53. Figure 11.15 Growth factor Receptor Reception Transduction CYTOPLASM Response Inactive transcription factor Active transcription factor DNA NUCLEUS mRNA Gene Phosphorylation cascade P
- 54. • Other pathways regulate the activity of enzymes rather than their synthesis © 2011 Pearson Education, Inc.
- 55. Figure 11.16 Reception Transduction Response Binding of epinephrine to G protein-coupled receptor (1 molecule) Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102 ) ATP Cyclic AMP (104 ) Inactive protein kinase A Active protein kinase A (104 ) Inactive phosphorylase kinase Active phosphorylase kinase (105 ) Inactive glycogen phosphorylase Active glycogen phosphorylase (106 ) Glycogen Glucose 1-phosphate (108 molecules)
- 56. • Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape © 2011 Pearson Education, Inc.
- 57. Wild type (with shmoos) Fus3 formin Mating factor activates receptor. Mating factor G protein-coupled receptor Shmoo projection forming Formin G protein binds GTP and becomes activated. 2 1 3 4 5 P P P P Formin Formin Fus3 Fus3 Fus3 GDP GTP Phosphory- lation cascade Microfilament Actin subunit Phosphorylation cascade activates Fus3, which moves to plasma membrane. Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. RESULTS CONCLUSION Figure 11.17
- 58. Fine-Tuning of the Response • There are four aspects of fine-tuning to consider – Amplification of the signal (and thus the response) – Specificity of the response – Overall efficiency of response, enhanced by scaffolding proteins – Termination of the signal © 2011 Pearson Education, Inc.
- 59. Signal Amplification • Enzyme cascades amplify the cell’s response • At each step, the number of activated products is much greater than in the preceding step © 2011 Pearson Education, Inc.
- 60. The Specificity of Cell Signaling and Coordination of the Response • Different kinds of cells have different collections of proteins • These different proteins allow cells to detect and respond to different signals • Even the same signal can have different effects in cells with different proteins and pathways • Pathway branching and “cross-talk” further help the cell coordinate incoming signals © 2011 Pearson Education, Inc.
- 61. Figure 11.18 Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Response 4 Response 5 Activation or inhibition Cell B. Pathway branches, leading to two responses. Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.
- 62. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins are large relay proteins to which other relay proteins are attached • Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway • In some cases, scaffolding proteins may also help activate some of the relay proteins © 2011 Pearson Education, Inc.
- 64. Termination of the Signal • Inactivation mechanisms are an essential aspect of cell signaling • If ligand concentration falls, fewer receptors will be bound • Unbound receptors revert to an inactive state © 2011 Pearson Education, Inc.
- 65. Apoptosis integrates multiple cell-signaling pathways • Apoptosis is programmed or controlled cell suicide • Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells • Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells © 2011 Pearson Education, Inc.
- 66. Apoptosis in the Soil Worm Caenorhabditis elegans • Apoptosis is important in shaping an organism during embryonic development • The role of apoptosis in embryonic development was studied in Caenorhabditis elegans • In C. elegans, apoptosis results when proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis © 2011 Pearson Education, Inc.
- 67. Figure 11.21 Mitochondrion Ced-9 protein (active) inhibits Ced-4 activity Receptor for death- signaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Death- signaling molecule Ced-9 (inactive) Cell forms blebs Active Ced-4 Active Ced-3 Other proteases Nucleases Activation cascade (b) Death signal
- 68. Apoptotic Pathways and the Signals That Trigger Them • Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis • Apoptosis can be triggered by – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum © 2011 Pearson Education, Inc.
- 69. • Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals • Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers © 2011 Pearson Education, Inc.
Editor's Notes
- #3: Figure 11.1 How does cell signaling trigger the desperate flight of this gazelle?
- #6: Figure 11.2 Communication between mating yeast cells.
- #8: Figure 11.3 Communication among bacteria.
- #10: Figure 11.4 Communication by direct contact between cells.
- #12: Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals.
- #13: Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals.
- #16: Figure 11.6 Overview of cell signaling.
- #17: Figure 11.6 Overview of cell signaling.
- #18: Figure 11.6 Overview of cell signaling.
- #22: Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors
- #23: Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors
- #25: Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors
- #27: Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors
- #29: Figure 11.9 Steroid hormone interacting with an intracellular receptor.
- #30: Figure 11.9 Steroid hormone interacting with an intracellular receptor.
- #31: Figure 11.9 Steroid hormone interacting with an intracellular receptor.
- #32: Figure 11.9 Steroid hormone interacting with an intracellular receptor.
- #33: Figure 11.9 Steroid hormone interacting with an intracellular receptor.
- #38: Figure 11.10 A phosphorylation cascade.
- #41: Figure 11.11 Cyclic AMP.
- #43: Figure 11.12 cAMP as a second messenger in a G protein signaling pathway.
- #45: Figure 11.13 The maintenance of calcium ion concentrations in an animal cell.
- #48: Figure 11.14 Calcium and IP3 in signaling pathways.
- #49: Figure 11.14 Calcium and IP3 in signaling pathways.
- #50: Figure 11.14 Calcium and IP3 in signaling pathways.
- #53: Figure 11.15 Nuclear responses to a signal: the activation of a specific gene by a growth factor.
- #55: Figure 11.16 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine.
- #57: Figure 11.17 Inquiry: How do signals induce directional cell growth during mating in yeast?
- #61: Figure 11.18 The specificity of cell signaling.
- #63: Figure 11.19 A scaffolding protein.
- #67: Figure 11.21 Molecular basis of apoptosis in C. elegans.