![Figure 11.13
Endoplasmic
reticulum (ER)
Plasma
membrane
Mitochondrion
ATP
ATP
ATPCYTOSOL
Nucleus
Ca2+
pump
EXTRACELLULAR
FLUID
Key High [Ca2+
] Low [Ca2+
]](https://image.slidesharecdn.com/chapter11-cellcommunication-151125145000-lva1-app6892/85/Chapter-11-Cell-Communication-37-320.jpg)
Chapter 11: Cell Communication
- 1. Chapter 11. Cell Communication • Cell-to-cell communication is essential for multicellular organisms • Biologists have discovered some universal mechanisms of cellular regulation
- 2. Evolution of Cell Signaling • 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 • Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and have since been adopted by eukaryotes Video: Common signaling mechanisms • Microbes are a window on the role of cell signaling in the evolution of life
- 3. Figure 11.2-3 Yeast cell, mating type a Exchange of mating factors Receptor a factor Yeast cell, mating type α a α 1 a α 2 Mating 3 New a/α cell a/ α α factor The molecular details of signal transduction in yeast and mammals are strikingly similar
- 4. Local and Long-Distance Signaling • Cells in a multicellular organisms 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. • Cell signaling is also critical in the microbial world. A concentration of signaling molecules allows bacteria to sense local population density in a process called quorum sensing.
- 5. Figure 11.4 Plasma membranes Cell wall (a) Cell junctions (b) Cell-cell recognition Gap junctions between animal cells Plasmodesmata between plant cells
- 6. Figure 11.5 Local signaling Target cells Secreting cell Secretory vesicles Local regulator Target cell (b) Synaptic signaling(a) Paracrine signaling (c) Endocrine (hormonal) signaling Electrical signal triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Long-distance signaling Endocrine cell Target cell specifically binds hormone. Hormone travels in bloodstream. Blood vessel •In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances: paracrine signaling •In long-distance signaling, plants and animals use chemicals called hormones
- 7. Regional specificity of induction in the chick Instructive mesenchyme
- 8. 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
- 9. Figure 11.6-1 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1
- 10. Figure 11.6-2 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1 Transduction2 Relay molecules 1 2 3
- 11. Figure 11.6-3 CYTOPLASM Plasma membrane EXTRACELLULAR FLUID Receptor Signaling molecule Reception1 Transduction2 Relay molecules 1 2 3 Response3 Activation of cellular response GAME TIME
- 12. Reception: A signal molecule binds to a receptor protein, causing it to change shape • The binding between a signal molecule (ligand) and receptor is highly specific • A conformational change in a receptor is often the initial transduction of the signal • Most signal receptors are plasma membrane proteins
- 13. Intracellular Receptors • Some receptor proteins are intracellular, 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
- 14. LE 11-6 EXTRACELLULAR FLUID Plasma membrane The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormone- receptor complex enters the nucleus and binds to specific genes. The bound protein stimulates the transcription of the gene into mRNA. The mRNA is translated into a specific protein. CYTOPLASM NUCLEUS DNA Hormone (testosterone) Receptor protein Hormone- receptor complex mRNA New protein
- 15. Receptors in the Plasma Membrane • Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane • There are three main types of membrane receptors: – G-protein-linked receptors – Receptor tyrosine kinases – Ion channel receptors
- 16. Segment that interacts with G proteins Signal-binding site G-protein-linked receptor •A G-protein-linked receptor 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
- 17. Figure 11.8b Activated enzyme Enzyme G protein (inactive)CYTOPLASM G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule GDP GTP GDP GTP GDP Inactive enzyme Cellular response P i GTP GDP 1 2 43
- 18. •Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines •A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Tyr Tyr Tyr Tyr Tyr Tyr Ligand-binding site α helix in the membrane Signaling molecule (ligand) Signaling molecule Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Inactive relay proteins Cellular response 1 Cellular response 2 P P P P P P P P P P P P Tyr Tyr Tyr Fully activated receptor tyrosine kinase (phos- phorylated dimer) Tyr Tyr Tyr Tyr Tyr Tyr 6 6 ADPATP Activated tyrosine kinase regions (unphosphorylated dimer) 1 2 43
- 19. Structure and function of a receptor tyrosine kinase
- 20. Activation of the Mitf transcription factor through the binding of stem cell factor by the Kit RTK protein (Part 2) 2nd example of RTK(Kit)
- 21. Two signals (juxtacrine) are needed to effect the differentiation of the T lymphocyte
- 22. Signal molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate closed Gate open Cellular response An 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
- 23. 1. Which choice CORRECTLY describes what happens during the transduction part of a signal transduction response pathway? a. Some fraction of the original signal is converted into something else and passed through the cell. b. Changes in protein activities and in other items in the cell are induced by an activated receptor. c. The original signal is amplified as it is passed through the cell. d. Energy from the signal is used to power the changes needed in the cell for a response. e. Some phenotypic feature of the cell is altered.
- 24. 1. Which choice CORRECTLY describes what happens during the transduction part of a signal transduction response pathway? a. Some fraction of the original signal is converted into something else and passed through the cell. b. Changes in protein activities and in other items in the cell are induced by an activated receptor. c. The original signal is amplified as it is passed through the cell. d. Energy from the signal is used to power the changes needed in the cell for a response. e. Some phenotypic feature of the cell is altered.
- 25. 2. Of the following events, which might typically occur THIRD in the course of a cell’s receiving and responding to a signal? a. An enzyme cascade occurs, increasing the number of activated proteins. b. A signal molecule is bound by a transmembrane tyrosine kinase receptor protein. c. The receptor protein complex phosphorylates other proteins. d. A reconfigured protein binds to DNA, altering gene expression. e. Tyrosine kinase receptor subunits dimerize.
- 26. 2. Of the following events, which might typically occur THIRD in the course of a cell’s receiving and responding to a signal? a. An enzyme cascade occurs, increasing the number of activated proteins. b. A signal molecule is bound by a transmembrane tyrosine kinase receptor protein. c. The receptor protein complex phosphorylates other proteins. d. A reconfigured protein binds to DNA, altering gene expression. e. Tyrosine kinase receptor subunits dimerize. f. B->e->c->a->d
- 27. Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • 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
- 28. 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 conformational change
- 29. Protein Phosphorylation and Dephosphorylation • In many pathways, the signal is transmitted by a cascade of protein phosphorylations (protein kinases transfer PO4 from ATP to protein) • Phosphatase enzymes remove the phosphates • This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off
- 30. Figure 11.10 Signaling molecule Activated relay molecule Receptor Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Active protein Inactive protein Phosphorylation cascade ATP ADP PP ATP ADP P i P P P i ATP ADP PP PP P i P Cellular response
- 31. Small Molecules and Ions as Second Messengers • Second messengers are small, nonprotein, water-soluble molecules or ions; Calcium ions and cyclic AMP are common second messengers • The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger” • Second messengers can readily spread throughout cells by diffusion • Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases
- 32. ATP Cyclic AMP AMP Adenylyl cyclase Pyrophosphate P P i Phosphodiesterase H2O 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
- 33. • Many signal molecules trigger formation of cAMP • Other components of cAMP pathways are G proteins, G-protein-linked 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
- 34. Figure 11.12 First messenger (signaling molecule such as epinephrine) G protein Adenylyl cyclase G protein-coupled receptor Second messenger Cellular responses Protein kinase A GTP ATP cAMP
- 35. • Understanding of the role of cAMP in G protein signaling pathways helps explain how certain microbes cause disease • The cholera bacterium, Vibrio cholerae, produces a toxin that modifies a G protein so that it is stuck in its active form • This modified G protein continually makes cAMP, causing intestinal cells to secrete large amounts of salt into the intestines • Water follows by osmosis and an untreated person can soon die from loss of water and salt
- 36. 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
- 37. Figure 11.13 Endoplasmic reticulum (ER) Plasma membrane Mitochondrion ATP ATP ATPCYTOSOL Nucleus Ca2+ pump EXTRACELLULAR FLUID Key High [Ca2+ ] Low [Ca2+ ]
- 38. • 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 • These two are produced by cleavage of a certain phospholipid in the plasma membrane
- 39. Figure 11.14-1 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen
- 40. Figure 11.14-2 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen Ca2+ (second messenger)
- 41. Figure 11.14-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP CYTOSOL G protein-coupled receptor Phospholipase C DAG PIP2 IP3 (second messenger) IP3-gated calcium channel Ca2+ Nucleus Endoplasmic reticulum (ER) lumen Ca2+ (second messenger) Various proteins activated Cellular responses
- 42. Cytoplasmic and Nuclear Responses • Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities • The response may occur in the cytoplasm or may involve action in the nucleus • Many pathways regulate the activity of enzymes via gene expression control
- 43. Figure 11.16 Reception Transduction 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 ) Active glycogen phosphorylase (106 ) Inactive glycogen phosphorylase Glycogen Response Glucose 1-phosphate (108 molecules) Binding of epinephrine to G protein-coupled receptor (1 molecule)
- 44. • Many other signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus • The final activated molecule may function as a transcription factor
- 46. Fine-Tuning of the Response • Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response 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
- 47. The Specificity of Cell Signaling • Different kinds of cells have different collections of proteins • These differences in proteins give each kind of cell specificity in detecting and responding to signals • The response of a cell to a signal depends on the cell’s particular collection of proteins • Pathway branching and “cross-talk” further help the cell coordinate incoming signals
- 48. Figure 11.17 Signaling molecule Receptor Relay mole- cules Response 1 Response 2 Response 3 Response 4 Response 5 Cell A: Pathway leads to a single response. 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. Activation or inhibition
- 49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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 Signaling molecule Receptor Scaffolding protein Plasma membrane Three different protein kinases
- 50. Termination of the Signal • Inactivation mechanisms are an essential aspect of cell signaling • When signal molecules leave the receptor, the receptor reverts to its inactive state
- 51. 3. Which of the following INCORRECTLY describes an aspect of the use of a second messenger in a typical signal transduction pathway? a. The second messenger can diffuse rapidly through the cytosol. b. After the rise in the concentration of the second messenger, it is often removed quickly by degradation or export from the cytosol. c. The proteins that will bind the second messenger are already present before there is a rise in its concentration. d. Synthesis of the enzyme that creates the second messenger occurs right after the signal is received, and not before. e. When the cell does not receive the signal, the second messenger is kept at a low concentration.
- 52. 3. Which of the following INCORRECTLY describes an aspect of the use of a second messenger in a typical signal transduction pathway? a. The second messenger can diffuse rapidly through the cytosol. b. After the rise in the concentration of the second messenger, it is often removed quickly by degradation or export from the cytosol. c. The proteins that will bind the second messenger are already present before there is a rise in its concentration. d. Synthesis of the enzyme that creates the second messenger occurs right after the signal is received, and not before. e. When the cell does not receive the signal, the second messenger is kept at a low concentration.
- 53. Concept 11.5: Apoptosis integrates multiple cell-signaling pathways • Cells that are infected or damaged or have reached the end of their functional lives often undergo “programmed cell death” • Apoptosis is the best understood type • 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
- 55. Apoptosis in the Soil Worm Caenorhabditis elegans • In worms and other organisms, apoptosis is triggered by signals that activate a cascade of “suicide” proteins in the cells programmed to die • When the death signal is received, an apoptosis inhibiting protein (Ced-9) is inactivated, triggering a cascade of caspase proteins that promote apoptosis • The chief caspase in the nematode is called Ced-3
- 56. Figure 11.20 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- signaling molecule (a) No death signal (b) Death signal Ced-4 Ced-3 Inactive proteins Death- signaling molecule Ced-9 (inactive) Active Ced-4 Active Ced-3 Cell forms blebs Other proteases Nucleases Activation cascade
- 57. Apoptotic Pathways and the Signals That Trigger Them • In humans and other mammals, several different pathways, including about 15 caspases, can carry out apoptosis • Apoptosis can be triggered by signals from outside the cell or inside it • Internal signals can result from irreparable DNA damage or excessive protein misfolding
- 58. • Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals • For example, apoptosis is a normal part of development of hands and feet in humans (and paws in other mammals) • Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers
- 59. Figure 11.21 Interdigital tissue 1 mm Cells undergoing apoptosis Space between digits
Editor's Notes
- #4: Figure 11.2-3 Communication between mating yeast cells (step 3)
- #6: Figure 11.4 Communication by direct contact between cells
- #7: Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals
- #8: devbio8e-fig-06-07-0.jpg
- #10: Figure 11.6-1 Overview of cell signaling (step 1)
- #11: Figure 11.6-2 Overview of cell signaling (step 2)
- #12: Figure 11.6-3 Overview of cell signaling (step 3)
- #18: Figure 11.8b Exploring cell-surface transmembrane receptors (part 2: GPCR signaling)
- #20: devbio8e-fig-06-10-0.jpg
- #21: devbio8e-fig-06-13-2.jpg
- #22: devbio8e-fig-06-37-0.jpg
- #24: Answer: B
- #25: Answer: B
- #26: Answer: C Order: 1) b, 2) e, 3) c, 4) a, 5) d.)
- #27: Answer: C Order: 1) b, 2) e, 3) c, 4) a, 5) d.)
- #31: Figure 11.10 A phosphorylation cascade
- #35: Figure 11.12 cAMP as a second messenger in a G protein signaling pathway
- #38: Figure 11.13 The maintenance of calcium ion concentrations in an animal cell
- #40: Figure 11.14-1 Calcium and IP3 in signaling pathways (step 1)
- #41: Figure 11.14-2 Calcium and IP3 in signaling pathways (step 2)
- #42: Figure 11.14-3 Calcium and IP3 in signaling pathways (step 3)
- #44: Figure 11.16 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine (adrenaline)
- #46: Figure 11.15 Nuclear responses to a signal: the activation of a specific gene by a growth factor
- #49: Figure 11.17 The specificity of cell signaling
- #52: Answer: D
- #53: Answer: D
- #55: Figure 11.19 Apoptosis of a human white blood cell
- #57: Figure 11.20 Molecular basis of apoptosis in C. elegans
- #60: Figure 11.21 Effect of apoptosis during paw development in the mouse