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Chapter 11 Cell Communication Cell Communication
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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
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Cells Recognize and Respond to External Signals
Microbes provide a glimpse of the role of cell signaling in the evolution of life
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Evolution of Cell Signaling
factor Receptor 1 Exchange of mating factors a The yeast, Saccharomyces cerevisiae, has two mating types, a and different mating types locate each other via secreted factors 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 a factor Yeast cell, mating type a Yeast cell, mating type 2 Mating a 3 New a/ cell a/
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Communication in Bacteria: Cell Signaling
1 Individual rod-shaped cells 2 Aggregation in progress 0.5 mm 3 Spore-forming structure (fruiting body) 2.5 mm Figure 11.3 Communication among bacteria. Quorum sensing to signal other cells to gather! Fruiting bodies
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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
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Gap junctions between animal cells Plasmodesmata between plant cells
Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions Figure 11.4 Communication by direct contact between cells. (b) Cell-cell recognition
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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
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Local Signaling Local Regulators: work over very short distances
Target cell Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Secreting cell Secretory vesicle Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals. Local regulator diffuses through extracellular fluid. Target cell is stimulated. (a) Paracrine signaling (b) Synaptic signaling
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Long Distance Signaling
Endocrine cell Blood vessel Hormones are used in long-distance signaling. Both plants and animals have hormones! AKA endocrine signaling Hormone travels in bloodstream. Target cell specifically binds hormone. Figure 11.5 Local and long-distance cell signaling by secreted molecules in animals. (c) Endocrine (hormonal) signaling
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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
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Animation: Overview of Cell Signaling Right-click slide / select “Play”
© 2011 Pearson Education, Inc. 12
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Reception: A cell recognizes the signal!
What determines if a cell will respond to a signal? EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception Receptor Figure 11.6 Overview of cell signaling. Signaling molecule
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Transduction: Converting the Signal to Action
EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling. Signaling molecule
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Response: Specific Cellular Action
EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling. Signaling molecule
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Reception: Signaling molecule and Receptor Proteins
The binding between a signal molecule (ligand) and receptor is highly specific
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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
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Type 1: G-protein Coupled Receptors
Signaling molecule binding site G protein-coupled receptors (GPCRs) are the largest family of cell- surface receptors 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
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G-protein Function: “On” and “Off”
G protein-coupled receptor Plasma membrane Activated receptor Signaling molecule Inactive enzyme GTP GDP GDP CYTOPLASM G protein (inactive) Enzyme GTP 1 2 GDP Activated enzyme Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors GTP GDP P i 3 Cellular response 4 Energy source GTP turns on the G protein GDP turns it off
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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
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RTK – Activation Through Dimerization
Signaling molecule (ligand) Ligand-binding site helix in the membrane Signaling molecule Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Dimer 1 2 Activated relay proteins Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors Cellular response 1 Tyr Tyr P Tyr Tyr P Tyr P Tyr P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Cellular response 2 Tyr Tyr P Tyr Tyr P Tyr Tyr P 6 ATP 6 ADP P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Inactive relay proteins 3 4
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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
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Ligand-Gated Ion Channel Activation
1 2 3 Gate closed Ions Gate open Gate closed Signaling molecule (ligand) Plasma membrane Ligand-gated ion channel receptor Cellular response Figure 11.7 Exploring: Cell-Surface Transmembrane Receptors Signaling molecule binds to allow specific ions into cell These ions produce cellular responses (Ca+2 one of the most important!)
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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
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Hormone Activation The signaling molecule is permeable to the membrane
Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein The signaling molecule is permeable to the membrane The receptor is found inside the cell DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM
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Hormone Activation Hormone and receptor bond, activating the complex
Figure Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone and receptor bond, activating the complex Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM
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Hormone Activation Figure Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein One possible function of these complexes are to initiate the synthesis of specific genes Here the complex enters the nucleus , acting as a transcription factor Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. NUCLEUS CYTOPLASM
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Hormone Activation Figure Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein The target RNA is made and exported for protein production Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. mRNA NUCLEUS CYTOPLASM
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Hormone Activation Figure Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Target protein is synthesized, completing the initial signal’s response Hormone- receptor complex DNA Figure 11.9 Steroid hormone interacting with an intracellular receptor. mRNA NUCLEUS New protein CYTOPLASM
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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
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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
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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
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Activated relay molecule
Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP Active protein kinase 2 P PP P i Figure A phosphorylation cascade. Inactive protein kinase 3 ATP ADP P Active protein kinase 3 PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i
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Activated relay molecule
Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP Active protein kinase 2 P PP P i Inactive protein kinase 3 ATP Figure A phosphorylation cascade. ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein PP P i
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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
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Cyclic AMP: Activation
ATP is made into cAMP in response to an extracellular signal Adenylyl cyclase Pyrophosphate P P i ATP cAMP
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Cyclic AMP: Regulation
Phosphodiesterase H2O H2O Figure Cyclic AMP. cAMP AMP
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cAMP Pathway Many signal molecules trigger formation of cAMP
First messenger (signaling molecule such as epinephrine) Adenylyl cyclase 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 G-protein systems that inhibit adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP Protein kinase A Cellular responses
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Calcium Ions EXTRACELLULAR FLUID Plasma membrane Ca2 pump Calcium ions (Ca2+) act as a second messenger in many pathways Cells can regulate its concentration A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol ATP Mitochondrion Nucleus CYTOSOL Ca2 pump Endoplasmic reticulum (ER) Ca2 pump ATP Key High [Ca2 ] Low [Ca2 ]
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Calcium and Inositol Triphosphate
Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers
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Animation: Signal Transduction Pathways Right-click slide / select “Play”
© 2011 Pearson Education, Inc. 41
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Signaling molecule (first messenger)
EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Figure Calcium and IP3 in signaling pathways. Endoplasmic reticulum (ER) Ca2 CYTOSOL
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Signaling molecule (first messenger)
EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Figure Calcium and IP3 in signaling pathways. Endoplasmic reticulum (ER) Ca2 Ca2 (second messenger) CYTOSOL
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Signaling molecule (first messenger)
EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Figure Calcium and IP3 in signaling pathways. Various proteins activated Cellular responses Endoplasmic reticulum (ER) Ca2 Ca2 (second messenger) CYTOSOL
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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”
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Nuclear and Cytoplasmic Responses
Growth factor Reception Receptor Signal transduction pathways lead to regulation of cellular activities The response can be cytoplasm or in the nucleus Regulate synthesis of proteins, usually by turning genes on or off Molecules may function as a transcription factor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA
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Signals Can Regulate Overall Cell Behavior
Wild type (with shmoos) Fus3 formin CONCLUSION 1 Mating factor activates receptor. Mating factor Shmoo projection forming G protein-coupled receptor Formin P Fus3 Actin subunit GTP P GDP 2 Phosphory- lation cascade G protein binds GTP and becomes activated. Formin Formin Figure Inquiry: How do signals induce directional cell growth during mating in yeast? P 4 Fus3 phos- phorylates formin, activating it. Microfilament Fus3 Fus3 P 5 Formin initiates growth of microfilaments that form the shmoo projections. 3 Phosphorylation cascade activates Fus3, which moves to plasma membrane.
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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
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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 At each step, the number of activated products is much greater than in the preceding step ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Figure Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine. Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose 1-phosphate (108 molecules)
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Fine Tuning 2: The Specificity of Cell Signaling and Coordination of the Response
Signaling molecule Receptor Relay molecules Activation or inhibition Figure The specificity of cell signaling. Response 1 Response 2 Response 3 Response 4 Response 5 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses. Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.
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Different kinds of cells have different collections of proteins
Signaling molecule Different kinds of cells have different collections of proteins Respond to different signals Same signal can have different effects in cells Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.
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Pathway branching and “cross-talk” further help the cell coordinate incoming signals
Activation or inhibition Figure The specificity of cell signaling. Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.
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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 Three different protein kinases Scaffolding protein
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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
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Signal Review 1 Reception 2 Transduction 3 Response Receptor
Activation of cellular response Relay molecules Figure 11.UN01 Summary figure, Concept 11.1 Signaling molecule
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