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Chapter 11

Chapter 11. Cell Communication. I. Evolution of Cell Signaling. Signal transduction pathway = steps by which a signal on a cell’s surface is converted into a cellular response Pathway similarities suggest signaling molecules evolved in prokaryotes and were modified later in eukaryotes.

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Chapter 11

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  1. Chapter 11 Cell Communication

  2. I. Evolution of Cell Signaling • Signal transduction pathway = steps by which a signal on a cell’s surface is converted into a cellular response • Pathway similarities suggest signaling molecules evolved in prokaryotes and were modified later in eukaryotes

  3. II. 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 • Local signaling = animal cells may communicate by direct contact (cell-cell recognition)

  4. Fig. 11-4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions (b) Cell-cell recognition

  5. Animal cells also communicate using local regulators, messenger molecules that travel only short distances • Long-distance signaling = plants and animals use hormones

  6. Fig. 11-5ab Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid Target cell is stimulated (a) Paracrine signaling (b) Synaptic signaling

  7. Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

  8. Cell Communication Intro (Andersen 10 min)

  9. III. Three Stages of Cell Signaling • Sutherland discovered how epinephrine acts on cells • Sutherland suggested that cells receiving signals went through three processes: • Reception • Transduction • Response

  10. Fig. 11-6-1 CYTOPLASM EXTRACELLULAR FLUID Plasma membrane Reception 1 1 Receptor Signaling molecule

  11. Fig. 11-6-2 CYTOPLASM EXTRACELLULAR FLUID Plasma membrane Reception Transduction 1 1 2 Receptor Relay molecules in a signal transduction pathway Signaling molecule

  12. Fig. 11-6-3 CYTOPLASM EXTRACELLULAR FLUID Plasma membrane Reception Transduction Response 1 2 3 Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule

  13. IV. Reception • Binding between a signal molecule (ligand) and receptor is highly specific • Shape change in a receptor is often the initial transduction (sending) of the signal • Most signal receptors are plasma membrane proteins

  14. V. Receptors in Membrane • Water-soluble signal molecules bind to receptor proteins in the plasma membrane • G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein • G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive

  15. Fig. 11-7a Signaling-molecule binding site Segment that interacts with G proteins G protein-coupled receptor

  16. Fig. 11-7b Plasma membrane Inactive enzyme G protein-coupled receptor Signaling molecule Activated receptor GDP GTP GDP Enzyme G protein (inactive) CYTOPLASM 2 1 Activated enzyme GTP GDP P i Cellular response 4 3

  17. Receptor tyrosine kinases are receptors that attach phosphates to tyrosines • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

  18. Fig. 11-7c Ligand-binding site Signaling molecule (ligand) Signaling molecule  Helix Tyr Tyr Tyr Tyr Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins Dimer CYTOPLASM 1 2 Activated relay proteins Cellular response 1 P P Tyr Tyr P Tyr Tyr Tyr Tyr P Tyr P Tyr P P Tyr Tyr Tyr Tyr P Cellular response 2 P P Tyr Tyr P Tyr Tyr Tyr Tyr P 6 ATP 6 ADP Activated tyrosine kinase regions Fully activated receptor tyrosine kinase Inactive relay proteins 4 3

  19. Ligand-gated ion channel receptor acts as a gate when the receptor changes shape • Signal molecule binds as a ligand to the receptor, the gate allows ions, such as Na+ or Ca2+, through a channel in the receptor

  20. Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane Ligand-gated ion channel receptor 2 Gate open Cellular response 3 Gate closed

  21. VI. Intracellular Receptors • Found in cytosol or nucleus of target cells • Small / hydrophobic chemical messengers can cross membrane and activate receptors • steroid and thyroid hormones of animals • Activated hormone-receptor complex can act as a transcription factor, turning on specific genes

  22. Fig. 11-8-1 EXTRACELLULAR FLUID Hormone (testosterone) Plasma membrane Receptor protein DNA NUCLEUS CYTOPLASM

  23. Fig. 11-8-2 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA NUCLEUS CYTOPLASM

  24. Fig. 11-8-3 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA NUCLEUS CYTOPLASM

  25. Fig. 11-8-4 EXTRACELLULAR FLUID Hormone (testosterone) Plasma membrane Receptor protein Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM

  26. Fig. 11-8-5 EXTRACELLULAR FLUID Hormone (testosterone) Plasma membrane Receptor protein Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM

  27. VII. Signal Transduction Pathways • Mostly proteins relay a signal from receptor to response • 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

  28. VIII. Protein Phosphorylation&Dephosphorylation • In many pathways, signal is transmitted by a cascade of protein phosphorylations • Protein kinases transfer phosphates from ATP to protein • Protein phosphatases remove the phosphates from proteins (dephosphorylation) • The phos and dephos system acts as a switch, turning activities on and off

  29. Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP P Active protein kinase 2 PP P i Inactive protein kinase 3 ATP ADP P Active protein kinase 3 PP P i Inactive protein ATP P ADP Active protein Cellular response PP P i

  30. IX. Second Messengers • The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” • Second messengers = small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion • Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases • Cyclic AMP and calcium ions are common second messengers

  31. A. Cyclic AMP • Cyclic AMP (cAMP) = one of most widely used • Adenylyl cyclase = enzyme in plasma memb, converts ATP to cAMP in response to an extracellular signal

  32. Fig. 11-10 Adenylyl cyclase Phosphodiesterase Pyrophosphate P P i ATP AMP cAMP

  33. 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

  34. Fig. 11-11 First messenger Adenylyl cyclase G protein GTP G protein-coupled receptor ATP Second messenger cAMP Protein kinase A Cellular responses

  35. B. Ca Ions and Inositol Triphosphate (IP3) • Calcium (Ca2+) is an important second messenger because cells can regulate its concentration

  36. Fig. 11-12 EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Ca2+ pump ATP Key High [Ca2+] Low [Ca2+]

  37. A signal relayed by a STP may trigger an inc in Ca in cytosol • Pathways leading to the release of Ca involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers

  38. Fig. 11-13-1 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Ca2+ CYTOSOL

  39. Fig. 11-13-2 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Ca2+ Ca2+ (second messenger) CYTOSOL

  40. Fig. 11-13-3 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Various proteins activated Cellular responses Ca2+ Ca2+ (second messenger) CYTOSOL

  41. Signal Transduction Pathways (Andersen 10min)

  42. X. Nuclear and Cytoplasmic Responses • Pathway leads to regulation of one or more cellular activities • Pathways regulate the synthesis of enzymes / proteins, by turning genes on / off in nucleus • Final molecule may function as a transcription factor

  43. Fig. 11-14 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA

  44. Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) • Other pathways regulate the activity of enzymes 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) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules)

  45. RESULTS Directional Growth in Yeast • Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape Wild-type (shmoos) ∆Fus3 ∆formin CONCLUSION Mating factor Shmoo projection forming G protein-coupled receptor Formin P Fus3 Actin subunit GTP P GDP Phosphory- lation cascade Formin Formin P Microfilament Fus3 Fus3 P

  46. XI. Fine-Tuning of the Response • Multistep pathways have two important benefits:

  47. A. 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

  48. B. Specificity and Coordination of the Response • Different kinds of cells have different collections of 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

  49. Fig. 11-17a Signaling molecule Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.

  50. Fig. 11-17b Activation or inhibition Response 4 Response 5 Cell D. Different receptor leads to a different response. Cell C. Cross-talk occurs between two pathways.

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