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Chapter 6a

Chapter 6a. Communication, Integration, and Homeostasis. About this Chapter. Cell-to-cell communication Signal pathways Novel signal molecules Modulation of signal pathways Control pathways Response loops Feedback loops. Cell-to-Cell Communication: Overview. Physiological signals

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Chapter 6a

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  1. Chapter 6a Communication, Integration,and Homeostasis

  2. About this Chapter • Cell-to-cell communication • Signal pathways • Novel signal molecules • Modulation of signal pathways • Control pathways • Response loops • Feedback loops

  3. Cell-to-Cell Communication: Overview • Physiological signals • Electrical signals • Changes in the membrane potential of a cell • Chemical signals • Secreted by cells into ECF • Responsible for most communication within the body • Target cells, or targets, receive signals • Four basic methods of communication

  4. Cell-to-Cell Communication: Methods • Direct contact and local cell-to-cell communication • Gap junctions • Transfer both chemical and electrical signals • Form direct cytoplasmic connections between adjacent cells. • Protein connexins form a connexon channel Figure 6-1a

  5. Cell-to-Cell Communication: Methods • CAMs, cell adhesion molecules, transfer signals in both directions • Common in Immune system • Contact-dependent signals require interaction between membrane molecules on two cells. Figure 6-1b

  6. Cell-to-Cell Communication: Methods • Direct contact and local cell-to-cell communication • Autocrine signals act on the same cell that secreted them. Paracrine signals are secreted by one cell and diffuse to adjacent cells. Receptor (c) Autocrine signals and paracrine signals Figure 6-1c

  7. Cell-to-Cell Communication: Methods • Paracrineand autocrineare chemical signals • Hormones are secreted by endocrine glands or cells into the blood. Only target cells with receptors for the hormone will respond to the signal. Blood Cell without receptor Cell with receptor Endocrine cell Target cell No response Response (a) Hormones Figure 6-2a

  8. Cell-to-Cell Communication: Methods • Long distance cell-to-cell communication • Neurotransmitters are chemicals secreted by neurons that diffuse across a small gap to the target cell. Neurons use electrical signals as well. • Neurotransmitters have a rapid effect Electrical signal Target cell Neuron (b) Neurotransmitters Figure 6-2b

  9. Cell-to-Cell Communication: Methods • Neurohormones are chemicals released by neurons into the blood for action at distant targets. Blood Neuron Cell without receptor Cell with receptor No response (c) Neurohormones Response Figure 6-2c

  10. Cell-to-Cell Communication: Methods • Cytokines may act as both local and long-distance signals • All nucleated cells synthesize and secrete cytokines in response to stimuli • In development and differentiation, cytokines usually function as autocrine or paracrine signals • In stress and inflammation, some cytokines may act on relatively distant targets

  11. Signal Pathways: Overview Signal molecule binds to Receptor protein activates Intracellular signal molecules alters Target proteins create Response Figure 6-3

  12. Signal Pathways: Receptor locations • Target cell receptors • Lipophilicvslipophobic Receptor in cytosol Receptor in nucleus Lipophilic signal molecules Lipophobic or lipophilic signal molecules Slower responses related to changes in gene activity Figure 6-4 (1 of 2)

  13. Signal Pathways: Receptor locations Lipophobic signal molecule Ligand-receptor complex Extracellular fluid Receptor Cell membrane Rapid cellular responses Intracellular fluid Figure 6-4 (2 of 2)

  14. Signal Pathways: Membrane Receptors • Four categories of membrane receptors Signal molecule Receptor Intracellular signal molecules Extracellular signal molecules ECF Integrin Channel Receptor Receptor Cell membrane Anchor protein G protein Enzyme ICF Cytoskeleton Receptor- channel Receptor-enzyme G protein-coupled receptor Integrin receptor Figure 6-5

  15. Signal Transduction Signal transduction converts one form of signal into a different form. External signal Radio waves Receptor Transducer Radio Amplifier Response Sound waves Figure 6-6

  16. Signal Pathways: Signal Amplification • Transducers convert extracellular signals into intracellular messages which create a response Receptor-ligand complex activates an amplifier enzyme (AE). Signal molecule Extracellular fluid Receptor Intracellular signal molecules Cell membrane Target proteins Intracellular fluid Figure 6-7

  17. Signal Pathways: Signal Amplification Table 6-1

  18. Signal Pathway: Biological Signal Transduction • Biological signal transduction converts chemical signals into cellular responses Signal molecule Extracellular fluid binds to Signal molecule Membrane receptor initiates Receptor Intracellular signal molecules Signal transduction by proteins Ion channel Target proteins Amplifier enzymes alter Response Second messenger molecules Intracellular fluid Increase intracellular Ca2+ Protein kinases Phosphorylated proteins Calcium-binding proteins Cell response Figure 6-8

  19. Signal Pathway: Signal Transduction • Steps of signal transduction pathway form a cascade Initial stimulus Active A Inactive A Active B Inactive B Active C Inactive C Substrate Product Figure 6-9

  20. Signal Pathway: Receptor Enzymes • Tyrosine kinase, an example of receptor-enzyme ECF Signal molecule binds to surface receptor Signal molecule Receptor activates Intracellular signal molecules Cell membrane Tyrosine kinase on cytoplasmic side Active binding site Phosphorylated protein Protein + Protein ATP + ADP ICF Figure 6-10

  21. Signal Pathway: GPCR • Membrane-spanning proteins • Cytoplasmic tail linked to G protein, a three-part transducer molecule • When G proteins are activated, they • Open ion channels in the membrane • Alter enzyme activity on the cytoplasmic side of the membrane

  22. GPCR: Adenylyl Cyclase-cAMP 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. One signal molecule 1 Adenylyl cyclase 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 2 3 ATP G protein 3 Adenylyl cyclase converts ATP to cyclic AMP. cAMP 4 4 cAMP activates protein kinase A. Protein kinase A 5 5 Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response. Phosphorylated protein Cell response Figure 6-11

  23. GPCR: Adenylyl Cyclase-cAMP 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. One signal molecule 1 G protein Figure 6-11, step 1

  24. GPCR: Adenylyl Cyclase-cAMP 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. One signal molecule 1 Adenylyl cyclase 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 2 G protein Figure 6-11, steps 1–2

  25. GPCR: Adenylyl Cyclase-cAMP 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. One signal molecule 1 Adenylyl cyclase 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 2 3 ATP G protein 3 Adenylyl cyclase converts ATP to cyclic AMP. cAMP Figure 6-11, steps 1–3

  26. GPCR: Adenylyl Cyclase-cAMP 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. One signal molecule 1 Adenylyl cyclase 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 2 3 ATP G protein 3 Adenylyl cyclase converts ATP to cyclic AMP. cAMP 4 4 cAMP activates protein kinase A. Protein kinase A Figure 6-11, steps 1–4

  27. GPCR: Adenylyl Cyclase-cAMP 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. One signal molecule 1 Adenylyl cyclase 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 2 3 ATP G protein 3 Adenylyl cyclase converts ATP to cyclic AMP. cAMP 4 4 cAMP activates protein kinase A. Protein kinase A 5 5 Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response. Phosphorylated protein Cell response Figure 6-11, steps 1–5

  28. GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 4 PL-C DAG PK-C Intracellular fluid Receptor Protein + Pi IP3 G protein 5 Phosphorylated Ca2+ stores Ca2+ protein KEY ER = PL-C phospholipase C = DAG diacylglycerol = PK-C protein kinase C Cellular = IP3 inositol trisphosphate response = ER endoplasmic reticulum 4 2 3 5 1 DAG activates protein kinase C (PK-C), which phosphorylates proteins. IP3 causes release of Ca2+ from organelles, creating a Ca2+ signal. Signal molecule activates receptor and associated G protein. G protein activates phospholipase C (PL-C), an amplifier enzyme. PL-C converts membrane phospholipids into diacylglycerol (DAG) which remains in the membrane, and IP3, which diffuses into the cytoplasm. Figure 6-12

  29. GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Cell membrane Intracellular fluid Receptor G protein KEY = PL-C phospholipase C = DAG diacylglycerol = PK-C protein kinase C = IP3 inositol trisphosphate = ER endoplasmic reticulum 1 Signal molecule activates receptor and associated G protein. Figure 6-12, step 1

  30. GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Cell membrane 2 PL-C Intracellular fluid Receptor G protein KEY = PL-C phospholipase C = DAG diacylglycerol = PK-C protein kinase C = IP3 inositol trisphosphate = ER endoplasmic reticulum 2 1 Signal molecule activates receptor and associated G protein. G protein activates phospholipase C (PL-C), an amplifier enzyme. Figure 6-12, steps 1–2

  31. GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 PL-C DAG Intracellular fluid Receptor IP3 G protein KEY = PL-C phospholipase C = DAG diacylglycerol = PK-C protein kinase C = IP3 inositol trisphosphate = ER endoplasmic reticulum 2 3 1 Signal molecule activates receptor and associated G protein. G protein activates phospholipase C (PL-C), an amplifier enzyme. PL-C converts membrane phospholipids into diacylglycerol (DAG) which remains in the membrane, and IP3, which diffuses into the cytoplasm. Figure 6-12, steps 1–3

  32. GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 4 PL-C DAG PK-C Intracellular fluid Receptor Protein + Pi IP3 G protein Phosphorylated protein KEY = PL-C phospholipase C = DAG diacylglycerol = PK-C protein kinase C Cellular = IP3 inositol trisphosphate response = ER endoplasmic reticulum 4 2 3 1 DAG activates protein kinase C (PK-C), which phosphorylates proteins. Signal molecule activates receptor and associated G protein. G protein activates phospholipase C (PL-C), an amplifier enzyme. PL-C converts membrane phospholipids into diacylglycerol (DAG) which remains in the membrane, and IP3, which diffuses into the cytoplasm. Figure 6-12, steps 1–4

  33. GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 4 PL-C DAG PK-C Intracellular fluid Receptor Protein + Pi IP3 G protein 5 Phosphorylated Ca2+ stores Ca2+ protein KEY ER = PL-C phospholipase C = DAG diacylglycerol = PK-C protein kinase C Cellular = IP3 inositol trisphosphate response = ER endoplasmic reticulum 4 2 3 5 1 DAG activates protein kinase C (PK-C), which phosphorylates proteins. IP3 causes release of Ca2+ from organelles, creating a Ca2+ signal. Signal molecule activates receptor and associated G protein. G protein activates phospholipase C (PL-C), an amplifier enzyme. PL-C converts membrane phospholipids into diacylglycerol (DAG) which remains in the membrane, and IP3, which diffuses into the cytoplasm. Figure 6-12, steps 1–5

  34. Signal Pathway: Receptor-Channel • Some second messengers create electrical signals Extracellular signal molecules Ions 1 G protein- coupled receptor Ion channel 2 G protein 3 Change in membrane permeability to Na+, K+, Cl– Intracellular signal molecules 1 Receptor-channels open or close in response to signal molecule binding. Creates electrical signal 2 Some channels are directly linked to G proteins. Voltage-sensitive protein 3 Other ligand-gated channels respond to intracellular second messengers. Cellular response Figure 6-13

  35. Signal Pathway: Receptor-Channel Extracellular signal molecules Ions 1 Ion channel 1 Receptor-channels open or close in response to signal molecule binding. Figure 6-13, step 1

  36. Signal Pathway: Receptor-Channel Extracellular signal molecules Ions 1 G protein- coupled receptor Ion channel 2 G protein 1 Receptor-channels open or close in response to signal molecule binding. 2 Some channels are directly linked to G proteins. Figure 6-13, steps 1–2

  37. Signal Pathway: Receptor-Channel Extracellular signal molecules Ions 1 G protein- coupled receptor Ion channel 2 G protein 3 Intracellular signal molecules 1 Receptor-channels open or close in response to signal molecule binding. 2 Some channels are directly linked to G proteins. 3 Other ligand-gated channels respond to intracellular second messengers. Figure 6-13, steps 1–3

  38. Signal Pathway: Receptor-Channel Extracellular signal molecules Ions 1 G protein- coupled receptor Ion channel 2 G protein 3 Change in membrane permeability to Na+, K+, Cl– Intracellular signal molecules 1 Receptor-channels open or close in response to signal molecule binding. Creates electrical signal 2 Some channels are directly linked to G proteins. Voltage-sensitive protein 3 Other ligand-gated channels respond to intracellular second messengers. Cellular response Figure 6-13

  39. Signal Pathway: Signal Transduction • Summary map of signal transduction systems Signal molecule Extracellular fluid Ions Membrane receptor Cell membrane Activates or inhibits amplifier enzyme Activates tyrosine kinase Activates G protein Gated ion channel alters Alters cytoskeleton alter produces phosphorylates Ions move into or out of cell Second messenger molecules Triggers release of Ca2+ from organelles Change in ion concentration activate creates bind to Electrical signal Protein kinases phosphorylate Altered proteins Intracellular fluid Cellular responses will be a change in Membrane receptors and transporters Gene activity and protein synthesis Motor proteins Enzyme activity Figure 6-14

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