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Transcript
Chapter 11 Cell Communication Cell Communication Overview: Cellular Messaging Cell-to-cell communication is essential for both multicellular and unicellular organisms Biologists have discovered some universal mechanisms of cellular regulation Cells most often communicate with each other via chemical signals For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine Cells Recognize and Respond to External Signals Microbes provide a glimpse of the role of cell signaling in the evolution of life Evolution of Cell Signaling The yeast, Saccharomyces cerevisiae, has two mating types, a and different mating types locate each other via secreted factors factor Receptor 1 Exchange of mating factors a a factor Yeast cell, Yeast cell, mating type a mating type 2 Mating a 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 3 New a/ cell a/ Communication in Bacteria: Cell Signaling 1 Individual rod-shaped cells 2 Aggregation in progress 0.5 mm 3 Spore-forming structure (fruiting body) Quorum sensing to signal other cells to gather! 2.5 mm Fruiting bodies Signaling in Multiceullar Organisms: “Local Signaling” Multicellular organism’s cells 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 Figure 11.4 Plasma membranes Gap junctions between animal cells (a) Cell junctions (b) Cell-cell recognition Plasmodesmata between plant cells In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal Local Signaling Local Regulators: work over very short distances Local signaling Electrical signal along nerve cell triggers release of neurotransmitter. Target cell Secreting cell Local regulator diffuses through extracellular fluid. (a) Paracrine signaling Neurotransmitter diffuses across synapse. Secretory vesicle Target cell is stimulated. (b) Synaptic signaling Long Distance Signaling Long-distance signaling Endocrine cell Blood vessel • Hormones are used in longdistance signaling. • Both plants and animals have hormones! • AKA endocrine signaling Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response Animation: Overview of Cell Signaling Right-click slide / select “Play” © 2011 Pearson Education, Inc. Reception: A cell recognizes the signal! What determines if a cell will respond to a signal? EXTRACELLULAR FLUID 1 Reception Receptor Signaling molecule CYTOPLASM Plasma membrane Transduction: Converting the Signal to Action EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Response: Specific Cellular Action EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Reception: Signaling molecule and Receptor Proteins The binding between a signal molecule (ligand) and receptor is highly specific Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane There are three main types of membrane receptors G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors Type 1: G-protein Coupled Receptors G protein-coupled receptors (GPCRs) are the largest family of cellsurface receptors Signaling molecule binding site Work 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 Segment that interacts with G proteins G protein-coupled receptor G-protein Function: “On” and “Off” G protein-coupled receptor Plasma membrane Activated receptor 1 Inactive enzyme GTP GDP GDP CYTOPLASM Signaling molecule Enzyme G protein (inactive) 2 GTP GDP Activated enzyme GTP GDP Pi 3 Cellular response 4 Energy source GTP turns on the G protein GDP turns it off Receptor Tyrosine Kinases Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Active form is a dimer Abnormal functioning of RTKs is associated with many types of cancers RTK – Activation Through Dimerization Signaling molecule (ligand) Ligand-binding site helix in the membrane Signaling molecule Tyrosines CYTOPLASM Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) 1 Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer 2 Activated relay proteins 3 Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P 6 ATP Activated tyrosine kinase regions (unphosphorylated dimer) 6 ADP Fully activated receptor tyrosine kinase (phosphorylated dimer) 4 Inactive relay proteins Cellular response 1 Cellular response 2 Ligand-Gated Ion Channels 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 Ligand-Gated Ion Channel Activation 1 Signaling molecule (ligand) 3 2 Gate closed Ions Plasma Ligand-gated membrane ion channel receptor Gate closed Gate open Cellular response Signaling molecule binds to allow specific ions into cell These ions produce cellular responses (Ca+2 one of the most important!) Intracellular Receptors: Hormones Intracellular receptor proteins are found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors steroid and thyroid hormones of animals Can act as a transcription factor, turning on specific genes Hormone Activation The signaling molecule is permeable to the membrane Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein The receptor is found inside the cell DNA NUCLEUS CYTOPLASM Figure 11.9-2 Hormone Activation Hormone and receptor bond, activating the complex Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Figure 11.9-3 Hormone Activation One possible function of these complexes are to initiate the synthesis of specific genes Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex Here the complex enters the nucleus , acting as a transcription factor DNA NUCLEUS CYTOPLASM Figure 11.9-4 Hormone Activation The target RNA is made and exported for protein production Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM Figure 11.9-5 Hormone Activation Target protein is synthesized, completing the initial signal’s response Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Transduction: Signal Transduction Cascades relay signals from receptors to target molecules in the cell Multistep pathways can amplify a signal and provide more opportunities for coordination and regulation of the cellular response Signal Transduction Pathways Proteins in the cytosol relay a signal from receptor Like dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein One of the most common methods of regulating the signal is through phosphorylation and dephosphorylation Protein Phosphorylation and Dephosphorylation: Molecular Switches Protein kinases transfer phosphates from ATP to protein phosphorylation Protein phosphatases remove the phosphates dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP P Active protein kinase 2 PP Pi Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP PP Pi Active protein Cellular response Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP P Active protein kinase 2 PP Pi Inactive protein kinase 3 ATP ADP Active protein kinase 3 PP Pi Inactive protein P ATP P ADP PP Pi Active protein Secondary Messengers: Small Molecules and Ions The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by GPCRs and RTKs Cyclic AMP and calcium ions are common second messengers Cyclic AMP: Activation • ATP is made into cAMP in response to an extracellular signal Adenylyl cyclase Pyrophosphate P ATP Pi cAMP Cyclic AMP: Regulation Phosphodiesterase H2O cAMP H2O AMP cAMP Pathway Many signal molecules trigger formation of cAMP cAMP usually activates protein kinase A, which phosphorylates various other proteins Regulation of cell metabolism is provided by Gprotein systems that inhibit adenylyl cyclase First messenger (signaling molecule such as epinephrine) G protein G protein-coupled receptor Adenylyl cyclase GTP ATP Second cAMP messenger Protein kinase A Cellular responses EXTRACELLULAR FLUID Plasma membrane Ca2 pump Mitochondrion ATP Calcium Ions Calcium ions (Ca2+) act as a second messenger in many pathways Nucleus Cells can regulate its concentration CYTOSOL Ca2 pump ATP Key High [Ca2 ] Ca2 pump Endoplasmic reticulum (ER) Low [Ca2 ] A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Calcium and Inositol Triphosphate Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers Animation: Signal Transduction Pathways Right-click slide / select “Play” © 2011 Pearson Education, Inc. EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca2 EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca2 Ca2 (second messenger) EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Ca2 Ca2 (second messenger) Cellular responses Response: Cell signaling leads to regulation of transcription or cytoplasmic activities •The cell’s response to an extracellular signal is sometimes called the “output response” Nuclear and Cytoplasmic Responses Growth factor Reception Receptor Signal transduction pathways lead to regulation of cellular activities Phosphorylation cascade Transduction The response can be cytoplasm or in the nucleus CYTOPLASM Regulate synthesis of proteins, usually by turning genes on or off Molecules may function as a transcription factor Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA Signals Can Regulate Overall Cell Behavior formin Fus3 Wild type (with shmoos) CONCLUSION 1 Mating factor activates receptor. Mating factor G protein-coupled Shmoo projection forming receptor Formin P Fus3 GDP GTP 2 G protein binds GTP and becomes activated. Fus3 Actin subunit P Phosphorylation cascade Fus3 Formin Formin P 4 Fus3 phosphorylates formin, activating it. P 3 Phosphorylation cascade activates Fus3, which moves to plasma membrane. Microfilament 5 Formin initiates growth of microfilaments that form the shmoo projections. Fine-Tuning of the Response There are four aspects of fine-tuning to consider Amplification of the signal (and thus the response) Specificity of the response Overall efficiency of response, enhanced by scaffolding proteins Termination of the signal Fine Tuning 1 Responses: Amplification of Signal Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) Enzyme cascades amplify the cell’s response ATP Cyclic AMP (104) At each step, the number of activated products is much greater than in the preceding step 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) Fine Tuning 2: The Specificity of Cell Signaling and Coordination of the Response Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Activation or inhibition Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Response 4 Cell C. Cross-talk occurs between two pathways. Response 5 Cell D. Different receptor leads to a different response. Signaling Different kinds of molecule cells have different collections of proteins Respond to different signals Same signal can have different effects in cells 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. Pathway branching and “cross-talk” further help the cell coordinate incoming signals Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways. Response 5 Cell D. Different receptor leads to a different response. Fine Tuning 3:Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins are large relay proteins to which other relay proteins are attached and can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway Signaling molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases Fine Tuning 4:Termination of the Signal Inactivation mechanisms are an essential aspect of cell signaling If ligand concentration falls, fewer receptors will be bound Unbound receptors revert to an inactive state Signal Review 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules Signaling molecule