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Transcript
CELL COMMUNICATION SIGNAL TRANSDUCTION PATHWAYS LOCAL 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 • In local signaling, animal cells may communicate by direct contact, or cell-cell recognition Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-4 Plasma membranes Gap junctions between animal cells (a) Cell junctions (b) Cell-cell recognition Plasmodesmata between plant cells Fig. 11-5ab Local signaling Target cell Secretin g 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 Target cell is stimulated (b) Synaptic signaling LONG-DISTANCE SIGNALING • In long-distance signaling, animals and plants use chemical messengers called hormones. • Hormones are chemicals made in one area of the body that are delivered to other areas. Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling WHAT ARE SIGNAL TRANSDUCTION PATHWAYS? • A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response. • In general there are 3 steps: • 1) Reception • 2) Transduction • 3) Response Fig. 11-6-1 EXTRACELLULAR FLUID 1 Reception Recepto r Signaling molecule CYTOPLASM Plasma membrane Fig. 11-6-2 CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Fig. 11-6-3 CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule STEP 1: RECEPTION • In Step 1, Reception: a signaling molecule binds to a receptor protein, causing it to change shape. • Ligand: the signaling molecule • Receptor: a molecule (usually a protein) on the surface of a cell that recognizes and binds to a ligand • The binding between a ligand and its’ receptor is highly specific. RECEPTORS IN THE PLASMA MEMBRANE • Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane • Examples of membrane receptors: • G protein-coupled receptors • Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings G-Protein-Coupled Receptors • A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein • The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7b Plasma membrane G proteincoupled receptor Activated receptor Signaling molecule GDP CYTOPLASM GDP Enzyme G protein (inactive) GTP 2 1 Activated enzyme GTP GDP Pi Cellular response 3 4 Inactive enzyme Ligand-gated Ion Channel Receptor • A ligand-gated ion channel receptor acts as a gate when the receptor changes shape • When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Plasma membran e Ligand-gated ion channel receptor 2 Ions Gate open Cellular response 3 Gate closed STEP 2: TRANSDUCTION • In Step 2, Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Transduction: the conversion of a signal outside the cell to a form that can bring about a specific cellular response. SIGNAL TRANSDUCTION PATHWAYS • Signal transduction usually involves multiple steps, called a signal cascade. • Multi-step pathways (signaling cascades) can amplify a signal; even just a few molecules can cause a large cell response. • Advantage: multi-step pathways can provide for more ways to coordinate and regulate the response. • Multi-step pathways also allow for more specificity in the response. Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Pi ADP P Active protein kinase 2 PP Inactive protein kinase 3 Pi ATP ADP Active protein kinase 3 PP Inactive protein ATP Pi PP ADP P P Active protein Cellular response SECOND MESSENGERS • The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” • Second messengers are small, non-protein, watersoluble molecules or ions that spread throughout a cell by diffusion • Second messengers participate in pathways initiated by G protein-coupled receptors • Cyclic AMP and calcium ions are common second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings CYCLIC AMP • Cyclic AMP (cAMP) is one of the most widely used second messengers • Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-10 Conversion of ATP to cAMP to AMP Adenylyl cyclase Phosphodiesterase Pyrophosphate P ATP Pi cAMP AMP Triggering the making of cAMP • Many signal molecules trigger formation of cAMP • cAMP usually activates protein kinase A, which phosphorylates various other proteins • Further regulation of cell metabolism is provided by Gprotein systems that inhibit adenylyl cyclase. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-11 First messenger Adenyly l cyclase G protein G proteincoupled receptor GTP ATP cAM P Second messenger Protein kinase A Cellular responses CALCIUM IONS • Calcium ions (Ca2+) act as a second messenger in many pathways • Calcium is an important second messenger because cells can regulate its concentration Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-12 EXTRACELLULAR FLUID Plasma membran e Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Key High [Ca2+] Low [Ca2+] Ca2+ pump STEP 3: RESPONSE • In Step 3, Response: Cell signaling leads to regulation of transcription or a change in the cell’s activities. This is sometimes called the “output response”. • Transcription: One of the processes involved in genes that determines which proteins will be made in the cell • Other cell signaling pathways may regulate the action of an enzyme. Fig. 11-14 Growth factor Receptor Receptio n Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gen e NUCLEUS mRNA Fig. 11-15 Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction The stimulation of glycogen breakdown by epinephrine: 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 Glycoge n Glucose-1-phosphate (108 molecules) This is an example of a phosphorylation cascade CHANGES IN SIGNAL TRANSDUCTION PATHWAYS • Changes in signal transduction pathways can alter cellular response. • For Example: Conditions where signal transduction is blocked or defective can be deleterious (bad), preventative, or prophylactic (good). Fig. 11-UN1 What would happen if one of the relay molecules was defective? 1 Reception 2 Transduction 3 Response Receptor Relay molecules Signaling molecul e Activation of cellular response QUESTION: HOW DOES CAFFEINE WORK ON THE BRAIN? • Caffeine has many effects on the body, but the most noticeable is that it keeps us awake. • The caffeine molecule is large and polar, so it doesn’t diffuse easily across the cell membrane. • Instead it binds to receptors on the surfaces of nerve cells in the brain. ADENOSINE • Adenosine (a nucleoside) accumulates in the brain when a person is under stress or has prolonged mental activity. • When it binds to a specific receptor in the brain, adenosine sets in motion a signal transduction pathway that results in reduced brain activity, which usually means drowsiness. CAFFEINE AND ADENOSINE • Caffeine has a 3-dimensional structure similar to adenosine and is able to bind to the adenosine receptor. • Because its binding does not activate the receptor, caffeine functions as a antagonist of adenosine signaling, with the result that the brain stays active. Caffeine Adenosine CAFFEINE • Because caffeine has bound to the adenosine receptor, the adenosine has little effect, and the person stays awake. • The binding of caffeine to the adenosine receptor, however, is a reversible reaction. In time, the caffeine molecules come off the adenosine receptors in the brain, allowing adenosine to bind once again. ADDITIONAL EFFECTS OF CAFFEINE • In addition to competing with adenosine for a membrane receptor, caffeine blocks the enzyme cAMP phosphodiesterase. • This enzyme breaks down cAMP, which is a second messenger in the pathway that turns glycogen into sugar which is then released into the bloodstream. • Can you see how caffeine increases the “fight or flight” response?