Chapter 11 Cell Communication 1 What is the

Figure 11. 3 Communication by direct contact between cells Plasma membranes Gap junctions between

Fig. 11. 6 Steroid hormone interacting with an intracellular receptor Hormone (testosterone) EXTRACELLULAR FLUID

Figure 11. 7 Exploring Membrane Receptors Signal-binding site G-PROTEIN-LINKED RECEPTORS Segment that interacts with

RECEPTOR TYROSINE KINASES Signal-binding site Signal molecule Helix in the Membrane Tyrosines Tyr Tyr

Signal molecule (ligand) Gate close Closed Ions Ligand-gated ion channel receptor Plasma Membrane Gate

Figure 11. 8 A phosphorylation cascade (involves several protein kinases) Signal molecule Receptor Activated

Fig 11. 10 c. AMP as a second messenger in a G-protein-signaling pathway First

Figure 11. 11 Maintenance of calcium ion concentrations in an animal cell EXTRACELLULAR FLUID

Figure 11. 12 Calcium and IP 3 in signaling pathways How does Ca+2 get

Figure 11. 12 Calcium and IP 3 in signaling pathways 1 A signal molecule

Figure 11. 13 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by

Figure 11. 14 Nuclear responses to a signal: the activation of a specific gene

Chapter 11: Cell Communication 1. 2. 3. 4. What is the difference between paracrine

Chapter 11: Cell Communication 1. 2. 3. 4. 5. What is the difference between

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Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? - Paracrine – local signaling from 1 cell to another in close range - Endocrine – long-distance signaling involving hormones Local signaling Long-distance signaling Target cell Secreting cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Endocrine cell Target cell is stimulated Blood vessel Hormone travels in bloodstream to target cells Target cell (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

Figure 11. 3 Communication by direct contact between cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? 2. What are the 3 stages of cell signaling? - Reception – ligand (signal molecule) binding to a receptor - Transduction – conversion of the received signal to a specific cellular response - Response – cell’s response to the signal EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule

Fig. 11. 6 Steroid hormone interacting with an intracellular receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex hormone testosterone passes through the plasma membrane. 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. 3 The hormonereceptor complex enters the nucleus and binds to specific genes. DNA m. RNA NUCLEUS 1 The non-polar steroid 4 The bound protein New protein stimulates the transcription of the gene into m. RNA. 5 The m. RNA is translated into a specific protein. CYTOPLASM

Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? 2. What are the 3 stages of cell signaling? 3. What are the 4 types of receptors? - Intracellular receptors…. . aka steroid hormone receptors - G-protein-linked receptors - Associated with a cytoplasmic G-protein - G-protein binds either GDP (inactive) or GTP (active) - Ligand binding - Causes a change in receptor shape which - Attracts the inactive G-protein - GTP displaces GDP activating the G-protein - Activated G-protein can then activate other specific molecules

Figure 11. 7 Exploring Membrane Receptors Signal-binding site G-PROTEIN-LINKED RECEPTORS Segment that interacts with G proteins G-protein-linked receptor Plasma Membrane Activated receptor Signal molecule GDP CYTOPLASM G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP Pi Cellular response Inactive enzyme

Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? 2. What are the 3 stages of cell signaling? 3. What are the 4 types of receptors? - Intracellular receptors…. . aka steroid hormone receptors - G-protein-linked receptors - Tyrosine kinase receptors - Kinase – enzyme that phosphorylates - Ligand binding - Causes receptor to form a dimer - Cytoplasmic tails phosphorylate each other because… - ATP is hydrolyzed & terminal phosphate is added to tyrosine aa - Activated receptors can then activate specific relay proteins

RECEPTOR TYROSINE KINASES Signal-binding site Signal molecule Helix in the Membrane Tyrosines Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Dimer Activated relay proteins Tyr Tyr P Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP Tyr P P Tyr Tyr P P Tyr P Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactive relay proteins Cellular response 1 Cellular response 2

Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? 2. What are the 3 stages of cell signaling? 3. What are the 4 types of receptors? - Intracellular receptors…. . aka steroid hormone receptors - G-protein-linked receptors - Tyrosine kinase receptors - Ligand-gated ion channels - Ligand binding - Causes a change in shape - Allows specific ions to move down concentration gradient - e. g. neurotransmitters between neurons

Signal molecule (ligand) Gate close Closed Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellular response Gate close ION CHANNEL RECEPTORS

Figure 11. 8 A phosphorylation cascade (involves several protein kinases) Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 1 A relay molecule activates protein kinase 1. ATP 5 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. ATP Pi ADP Active protein kinase 3 PP Inactive protein P 4 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. ATP ADP Pi PP de Inactive protein kinase 3 a sc ca PP on Pi 3 Active protein kinase 2 then catalyzes the phosphorylation (and activation) of protein kinase 3. P Active protein kinase 2 ADP i lat ory ph Inactive protein kinase 2 os Ph 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 1 P Active protein Cellular response

Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? 2. What are the 3 stages of cell signaling? - Reception – ligand (signal molecule) binding to a receptor - Transduction – conversion of the received signal to a specific cellular response - Often done by protein phosphorylations - 2 nd messengers - c. AMP – cyclic AMP – adenylyl cyclase converts ATP to c. AMP NH 2 N N O O O N N – O P O P O Ch 2 O O O N N O Pyrophosphate P Pi N N Adenylyl cyclase O OH OH ATP NH 2 O CH 2 Phoshodiesterase O P O O OH Cyclic AMP N N O HO P O CH 2 O O H 2 O OH OH AMP

Fig 11. 10 c. AMP as a second messenger in a G-protein-signaling pathway First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP c. AMP Second messenger Protein kinase A Cellular responses

Figure 11. 11 Maintenance of calcium ion concentrations in an animal cell EXTRACELLULAR FLUID Plasma membrane Ca 2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca 2+ pump ATP Ca 2+ Endoplasmic reticulum (ER) pump Key High [Ca 2+] Low [Ca 2+]

Figure 11. 12 Calcium and IP 3 in signaling pathways How does Ca+2 get released from the ER? - more 2 nd messengers - IP 3 - follow the numbers 1 A signal molecule binds 2 Phospholipase C cleaves a to a receptor, leading to plasma membrane phospholipid activation of phospholipase C. called PIP 2 into DAG and IP 3. EXTRACELLULAR FLUID 3 DAG functions as a second messenger in other pathways. Signal molecule (first messenger) G protein DAG GTP G-protein-linked receptor IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL 4 IP 3 quickly diffuses through the cytosol and binds to an IP 3– gated calcium channel in the ER membrane, causing it to open. Phospholipase C PIP 2 IP 3 (second messenger)

Figure 11. 12 Calcium and IP 3 in signaling pathways 1 A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRACELLULAR FLUID 2 Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. 3 DAG functions as a second messenger In other pathways. Signal molecule (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Ca 2+ (second messenger) 4 IP 3 quickly diffuses through the cytosol and binds to an IP 3– gated calcium channel in the ER membrane, causing it to open. 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca 2+ level in the cytosol. PIP 2 IP 3 (second messenger)

Figure 11. 12 Calcium and IP 3 in signaling pathways 1 A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRACELLULAR FLUID 2 Phospholipase C cleaves a plasma membrane phospholipid called PIP 2 into DAG and IP 3. 3 DAG functions as a second messenger in other pathways. Signal molecule (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Various proteins activated Ca 2+ CYTOSOL 4 IP 3 quickly diffuses through the cytosol and binds to an IP 3– gated calcium channel in the ER membrane, causing it to open. Cellular responses Ca 2+ (second messenger) 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca 2+ level in the cytosol. 6 The calcium ions activate the next protein in one or more signaling pathways.

Chapter 11: Cell Communication 1. What is the difference between paracrine signaling & endocrine signaling? 2. What are the 3 stages of cell signaling? - Reception – ligand (signal molecule) binding to a receptor - Transduction – conversion of the received signal to a specific cellular response - Often done by protein phosphorylations - Protein kinases phosphorylate other relay molecules (kinases) - Inactivated by phosphatases - 2 nd messengers - c. AMP – cyclic AMP – adenylyl cyclase converts ATP to c. AMP - Ca+2 ions - IP 3 - inositol triphosphate - Response – cell’s response to the signal 3. What is meant by signal amplification? - A single ligand can activate millions of molecules during a cell’s response

Figure 11. 13 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Reception - Cytoplasmic signal amplification Binding of epinephrine to G-protein-linked receptor (1 molecule) 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)

Figure 11. 14 Nuclear responses to a signal: the activation of a specific gene by a growth factor - Nuclear signal amplification Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS m. RNA

Chapter 11: Cell Communication 1. 2. 3. 4. What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What is meant my signal amplification? How can cells have different responses to the same signal? Signal - Different relay proteins molecule - Cross-talk w/ diff. signals - Different receptor types Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response Response 2 Response 3 Cell B. Pathway branches, leading to two responses Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways Response 5 Cell D. Different receptor leads to a different response

Chapter 11: Cell Communication 1. 2. 3. 4. 5. What is the difference between paracrine signaling & endocrine signaling? What are the 3 stages of cell signaling? What is meant my signal amplification? How can cells have different responses to the same signal? How do scaffolding proteins help cell communication? - By binding several different molecules together for quicker process Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases