Cytoplasm. Signal transduction pathway. environment. Cellular response. surface receptor. Signal transduction pathway.

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1 Module 2G: Cell Communication In this module, we will examine how the cells of a multicellular organism communicate with each other. Objective # 41 Explain how cells communicate with each other, and describe the following types of cell communication: a) direct contact b) paracine signaling c) endocrine signaling d) synaptic signaling 1 2 The cells of a multicellular organism communicate with each other using special signal molecules called ligands. To communicate, secretory cells release ligands that travel and bind to specific receptor proteins located either inside of target cells (intracellular receptors) or on the surface of target cells (surface receptors). When a ligand binds to its matching receptor, this triggers a series of events in the target cell. This series of events is called the signal transduction pathway and it produces some type of change or in the target cell. 3 4 External lasma membrane environment Overview of Cell Signaling: Hydrophilic ligand Hydrophobic ligand surface receptor Signal transduction pathway Cytoplasm intracellular receptor Cellular Signal transduction pathway Cellular Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. 5 Biologists recognize 4 types of cell signaling based mainly on the distance between the secretory and target cells: a) direct contact cells touch each other and signal molecules travel through special connections called communicating junctions: 6 1

2 Secretory cell Communicating junction b) paracine signaling signal molecules affect cells in the immediate vicinity: Direct contact Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. Target cell 7 8 Secretory cell Signal molecule l Adjacent target cells c) endocrine signaling signal molecules (called hormones) are released into the blood, which h carries them to distant target cells aracrine signaling Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display Hormone secretion into blood by endocrine gland Blood vessel Distant target cells Endocrine signaling Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. 11 d) synaptic signaling signal molecules (called neurotransmitters) cross a tiny space called the synaptic gap to reach the target cell 12 2

3 Neurotransmitter Objective # 42 Nerve cell Target cell Synaptic gap Describe the process of signal transduction. Synaptic signaling Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display Objective 42 Signal transduction refers to the events that are triggered within a target cell when a ligand binds to a receptor. The function of signal transduction is to produce some change in the behavior or nature of the target cell. This usually involves altering the composition or activity of cell proteins within the target cell. 15 Objective 42 Many cell proteins are inactive when initially synthesized. Some are activated by adding a phosphate group (phosphorylation) and then deactivated by removing a phosphate group (dephosphorylation). For other proteins, it s the reverse! 16 Objective 42 Enzymes that phosphorylate proteins using a phosphate from AT are called kinases and those that dephosphorylate proteins are called phosphatases. Generally, the phosphate group is added to or removed from one of 3 amino acids in the protein: serine, threonine, or tyrosine. Here we see a protein that is activated by phosphorylation and deactivated by dephosphorylation. Ser Tyr or Thr inactive protein AT AD Kinase OH i hosphatase Ser Tyr or Thr active protein O O O O 17 Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. 18 3

4 Objective # 43 Distinguish between intracellular receptors and cell surface receptors. Objective 43 Hydrophobic ligands can pass through the plasma membrane and bind to intracellular receptors (receptors located inside the cell.) Hydrophilic ligands generally cannot pass through the plasma membrane and bind to cell surface receptors (receptors embedded in the plasma membrane.) Objective # 44 Explain how the following types of intracellular receptors work: a) receptors that act as gene regulators b) receptors that act as enzymes Objective 44a Intracellular receptors that act as gene regulators: When the ligand joins to the receptor, the receptor changes shape and a DNA binding site is exposed. The DNA binding site joins to a specific segment of DNA and activates (or suppresses) a particular gene: Objective 44b Intracellular receptors that act as enzymes: These receptors catalyze (speed up) specific reactions within the cell. When a signal molecule joins to the receptor, the receptor s catalytic domain (region of the receptor that functions as an enzyme) is activated or deactivated. Many function as protein kinases. 24 4

5 Objective # 45 Explain how the following types of cell surface receptors work: a) chemically gated ion channels b) enzymatic receptors c) G-protein-coupled receptors Objective 45a Most signal receptors are cell surface receptors. We will examine 3 types of cell surface receptors : a) Chemically gated ion channels in these receptors, binding of a ligand causes an ion channel to open (or close) In this example, binding of ligands cause chemically gated ion channels to open: Ions Ligands (signal) Ions Lipid bilayer Chemically gated ion channel (open) Objective 45b b) Enzymatic receptors are enzymes that: are embedded in the plasma membrane, with their catalytic site (domain) exposed inside the cell and their receptor site (domain) exposed outside the cell have their catalytic domain activated when a ligand joins to the receptor site. Chemically gated ion channel (closed) Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display Binding of a ligand activates the catalytic domain of an enzymatic surface receptor: Lipid bilayer Inactive catalytic domain Cellular Receptor site Active catalytic domain Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. Ligand (signal) Enzymatic receptor 29 Objective 45b Enzymatic surface receptors usually function as protein kinases: When ligands join with the receptor, this activates the catalytic domain of the receptor. The catalytic domain then phosphorylates specific proteins within the cell, thereby activating or deactivating them. 30 5

6 Ligands Transmembrane RTK proteins Intracellular kinase domain Extracellular ligand-binding domain 1. Ligands bind to receptors. Dimerization and autophosphorylation 2. Two receptors associate and phosphorylate each other. hosphate groups Cellular hosphorylated protein 3. Receptors activate proteins by phosphorylating them. Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. Objective 45b The insulin receptor is an example of an enzymatic cell surface receptor. The role of insulin is to lower blood glucose level. When insulin binds to the insulin receptor, it triggers a series of events that activate the enzyme glycogen synthase, which converts glucose to glycogen. 32 Insulin receptor 2. α β Glycogen synthase α Glycogen β 4. Insulin Insulin protein Glucose Copyright The McGraw-Hill Companies, Inc. ermission required for reproduction or display. 1. Insulin binds to the extracellular domain of the insulin receptor. 2. The insulin receptor activates the insulin protein by phosphorylating it. 3. hosphorylated insulin protein activates glycogen synthase. 4. Glycogen synthase converts glucose into glycogen. Objective 45c c) G-protein-coupled receptors GCRs): These are the largest category of receptors in animal cells. The receptor is joined to a G-protein, which is made of 3 subunits: α,β,γ. γ When ligands bind to the receptor, the G protein is activated by exchanging GD for GT on the α subunit. The activated α subunit then separates from the β and γ subunits Objective 45c Once the α subunit of the G protein is activated, it may activate an effector protein (such as an enzyme or ion channel) that produces a direct cell. For example, the α subunit may trigger the opening of a chemically gated ion channel that allows Ca ++ ions to enter the cell: 36 6

7 Objective # 46 Discuss how second messengers may be used to relay a signal into a target cell, and explain how the relayed signal may be amplified Objective 46 As we have seen, when the α subunit of ag-protein activates a effector protein, the effector protein may produce a cellular directly. In other cases, the effector protein works by activating a second messenger, which transmits the message within the cell. The 2 most common second messengers are cam and Ca cam pathway: Objective 46 signal molecule binds to surface receptor surface receptor activates a G protein G G protein activates the membrane-bound bound enzyme, adenylyl cyclase adenylyl cyclase catalyzes synthesis of cam, which binds to a target protein target protein initiates cellular change 40 Objective 46 Ca ++ pathway: signal molecule binds to surface receptor surface receptor activates a G protein G G protein activates the membrane-bound bound enzyme, phospholipase C phospholipase C catalyzes synthesis of inositol triphosphate, which stimulates release of Ca ++ from ER released Ca ++ initiates cellular change initiates cellular change

8 Objective 46 Because of amplification at many steps in the cell signaling process, one signal molecule can ultimately trigger a relatively large by the target cell:

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