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POWERPOINT® LECTURE SLIDE PRESENTATION by LYNN CIALDELLA, MA, MBA, The University of Texas at Austin UNIT 1 6 PART A Communication, Integration, and Homeostasis HUMAN PHYSIOLOGY AN INTEGRATED APPROACH DEE UNGLAUB SILVERTHORN Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings FOURTH EDITION About this Chapter Cell-to-cell communication Signal pathways Novel signal molecules Modulation of signal pathways Control pathways Response loops Feedback loops Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cell-to-Cell Communication: Overview Physiological signals Electrical signals Changes in cell’s membrane potential 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 Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Cell-to-Cell Communication: Methods Direct contact and local cell-to-cell communication Gap junctions transfer both chemical and electrical signals Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-1a Cell-to-Cell Communication: Methods Direct contact and local cell-to-cell communication CAMs transfer signals in both directions Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-1b Cell-to-Cell Communication: Methods Paracrine and autocrine are chemical signals Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-1c Cell-to-Cell Communication: Methods Long distance cell-to-cell communication Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-2a Cell-to-Cell Communication: Methods Neurotransmitters have a rapid effect Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-2b Cell-to-Cell Communication: Methods Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-2c Signal Pathways: Overview Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-3 Signal Pathways: Receptor locations Target cell receptors Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-4 (1 of 2) Signal Pathways: Receptor locations Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-4 (2 of 2) Signal Pathways: Membrane Receptors Four categories of membrane receptors Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-5 Signal Pathways: Signal Amplification Transducers convert extracellular signals into intracellular messages which create a response Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-7 Signal Pathway: Biological Signal Transduction Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-8 Signal Pathway: Signal Transduction Steps of a cascade Steps of signal transduction pathway form a cascade Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-9 Signal Pathway: Receptor Enzymes Tyrosine kinase, an example of receptor-enzyme Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-10 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 Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings GPCR: Adenylyl Cyclase-cAMP The G proteincoupled adenylyl cyclasecAMP system G proteincoupled receptor 1 One signal molecule 2 Adenylyl cyclase 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 3 ATP 3 Adenylyl cyclase converts ATP to cyclic AMP. G protein cAMP 4 4 cAMP activates protein kinase A. 5 5 Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response. Protein kinase A Phosphorylated protein Cell response Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-11 GPCR: Adenylyl Cyclase-cAMP G proteincoupled receptor 1 One signal molecule 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. G protein Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-11, step 1 GPCR: Adenylyl Cyclase-cAMP G proteincoupled receptor 1 One signal molecule Adenylyl cyclase 2 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. 2 G protein turns on adenylyl cyclase, an amplifier enzyme. G protein Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-11, steps 1–2 GPCR: Adenylyl Cyclase-cAMP G proteincoupled receptor 1 One signal molecule 2 Adenylyl cyclase 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. 2 G protein turns on adenylyl cyclase, an amplifier enzyme. ATP 3 3 Adenylyl cyclase converts ATP to cyclic AMP. G protein cAMP Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-11, steps 1–3 GPCR: Adenylyl Cyclase-cAMP G proteincoupled receptor 1 One signal molecule 2 Adenylyl cyclase 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 3 ATP 3 Adenylyl cyclase converts ATP to cyclic AMP. G protein cAMP 4 Protein kinase A Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 4 cAMP activates protein kinase A. Figure 6-11, steps 1–4 GPCR: Adenylyl Cyclase-cAMP G proteincoupled receptor 1 One signal molecule 2 Adenylyl cyclase 1 Signal molecule binds to G protein-linked receptor, which activates the G protein. 2 G protein turns on adenylyl cyclase, an amplifier enzyme. 3 ATP 3 Adenylyl cyclase converts ATP to cyclic AMP. G protein cAMP 4 4 cAMP activates protein kinase A. 5 5 Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response. Protein kinase A Phosphorylated protein Cell response Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-11, steps 1–5 GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 PL-C 4 DAG PK-C Receptor Protein + Pi IP3 G protein Intracellular fluid 5 Ca2+ stores Phosphorylated protein Ca2+ ER Cellular response 1 Signal molecule 2 activates receptor and associated G protein. G protein activates 3 PL-C converts membrane 4 phospholipase C phospholipids into (PL-C), an amplifier diacylglycerol (DAG), which enzyme. remains in the membrane, and IP3, which diffuses into the cytoplasm. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings KEY PL-C DAG PK-C IP3 ER = = = = phospholipase C diacylglycerol protein kinase C inositol trisphosphate = endoplasmic reticulum DAG activates protein 5 kinase C (PK-C), which phosphorylates proteins. IP3 causes release of Ca2+ from organelles, creating a Ca2+ signal. Figure 6-12 GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Cell membrane Receptor Intracellular fluid G protein KEY PL-C DAG PK-C IP3 ER = = = = phospholipase C diacylglycerol protein kinase C inositol trisphosphate = endoplasmic reticulum 1 Signal molecule activates receptor and associated G protein. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-12, step 1 GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Cell membrane 2 PL-C Receptor Intracellular fluid G protein KEY PL-C DAG PK-C IP3 ER 1 Signal molecule 2 activates receptor and associated G protein. = = = = phospholipase C diacylglycerol protein kinase C inositol trisphosphate = endoplasmic reticulum G protein activates phospholipase C (PL-C), an amplifier enzyme. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-12, steps 1–2 GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid 3 2 PL-C Receptor G protein Cell membrane DAG Intracellular fluid IP3 KEY PL-C DAG PK-C IP3 ER 1 Signal molecule 2 activates receptor and associated G protein. = = = = phospholipase C diacylglycerol protein kinase C inositol trisphosphate = endoplasmic reticulum G protein activates 3 PL-C converts membrane phospholipase C phospholipids into (PL-C), an amplifier diacylglycerol (DAG), which enzyme. remains in the membrane, and IP3, which diffuses into the cytoplasm. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-12, steps 1–3 GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 PL-C 4 DAG PK-C Receptor G protein Protein + Pi IP3 Phosphorylated protein Cellular response 1 Signal molecule 2 activates receptor and associated G protein. G protein activates 3 PL-C converts membrane 4 phospholipase C phospholipids into (PL-C), an amplifier diacylglycerol (DAG), which enzyme. remains in the membrane, and IP3, which diffuses into the cytoplasm. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings KEY PL-C DAG PK-C IP3 ER Intracellular fluid = = = = phospholipase C diacylglycerol protein kinase C inositol trisphosphate = endoplasmic reticulum DAG activates protein kinase C (PK-C), which phosphorylates proteins. Figure 6-12, steps 1–4 GPCR: The Phospholipase C System Signal molecule Extracellular fluid 1 Membrane phospholipid Cell membrane 3 2 PL-C 4 DAG PK-C Receptor Protein + Pi IP3 G protein Intracellular fluid 5 Ca2+ stores Phosphorylated protein Ca2+ ER Cellular response 1 Signal molecule 2 activates receptor and associated G protein. G protein activates 3 PL-C converts membrane 4 phospholipase C phospholipids into (PL-C), an amplifier diacylglycerol (DAG), which enzyme. remains in the membrane, and IP3, which diffuses into the cytoplasm. Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings KEY PL-C DAG PK-C IP3 ER = = = = phospholipase C diacylglycerol protein kinase C inositol trisphosphate = endoplasmic reticulum DAG activates protein 5 kinase C (PK-C), which phosphorylates proteins. IP3 causes release of Ca2+ from organelles, creating a Ca2+ signal. Figure 6-12, steps 1–5 Signal Pathway: Receptor-Channel How ions create electrical signals Ions Extracellular signal molecules 1 Ion channel G proteincoupled receptor 2 G protein Change in membrane permeability to Na+, K+, Cl– 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 messenger. Creates electrical signal Voltage-sensitive protein Cellular response Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13 Signal Pathway: Receptor-Channel Ions Extracellular signal molecules 1 1 Receptor-channels open or close in response to signal molecule binding. Ion channel Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13, step 1 Signal Pathway: Receptor-Channel Ions Extracellular signal molecules 1 Ion channel 2 G proteincoupled receptor G protein Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 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 Signal Pathway: Receptor-Channel Ions Extracellular signal molecules 1 Ion channel 2 G proteincoupled receptor G protein 3 Intracellular signal molecules Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings 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 messenger. Figure 6-13, steps 1–3 Signal Pathway: Receptor-Channel Ions Extracellular signal molecules 1 Ion channel G proteincoupled receptor 2 G protein Change in membrane permeability to Na+, K+, Cl– 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 messenger. Creates electrical signal Voltage-sensitive protein Cellular response Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-13 Signal Pathway: Signal Transduction Summary map of signal transduction systems Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 6-14