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CELL Communication Chapter 11
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OUTLINE An overview of Cell signaling
A. Cell signaling evolved early in the history of life B. Communicating cells may be close or far apart C. Three stages of cell signaling are: reception, transduction, response
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OUTLINE II II. Signal reception and the Initiation of Transduction
A. A chemical receptor binds to a receptor protein, causing the receptor protein to change shape B. Most signal receptors are plasma-membrane proteins
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OUTLINE III III. Signal Transduction Pathways
A. Pathways relay signals from receptors to cellular responses B. Protein Phosphorylation is a major mechanism of signal transduction C. Certain small molecules and ions are key components of signaling pathways (second messengers)
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OUTLINE IV IV. Cellular Responses to Signals
A. In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus. B. Elaborate pathways amplify and specify the cell’s responses to signals
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Cell Signaling Evolved Early
Yeast mating is coordinated by chemical signaling Yeast have 2 mating types, a and alpha Type a cells secrete a-factor chemical signal, alpha cells secrete alpha factor The binding of a-factor to alpha cells and vice versa causes cells to move toward each other and fuse
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Yeast tie ins The steps by which yeast mating signals are converted into cell responses are similar to how prokaryotes, plants, animals chemical signals are converted to specific cell responses The Steps by which a chemical signal is converted into a cell response is called a signal transduction pathway
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Yeast Communication
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Communicating cells may be close or far
LOCAL REGULATOR: a chemical signal which communicates between 2 nearby cells PARACRINE SIGNALING: a cell secretes the signal into extracellular fluid, acts on nearby cell SYNAPTIC SIGNALING: a nerve cell releases a signal (ie. neurotransmitter) into a synapse. The target cells are other nerve cells or muscle cells
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Distance makes the heart grow fonder….
HORMONES: signal to cells which are some distance apart Examples: Ethylene in plants, insulin in animals
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Local and Distant Cell Communication
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Direct Contact Some animal and plant cells can communicate directly through junctions through which signals can travel between adjacent cells.
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Communication By Direct Contact
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Reception, Transduction, Response
In order for the signal to cause a response in a cell, that cell must have the proper signaling system. Cells without ignore the signal. RECEPTION: the signal binds to a specific cellular protein called a receptor, usually on the cell’s surface SIGNAL TRANSDUCTION: the binding causes a change in conformation, which then converts the signal into a cell response CELLULAR RESPONSE: the transduction system causes a specific cell response, ie. Altered gene expression, enzyme activation
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Signal Reception and the Initiation of Transduction
A chemical signal binds to a receptor protein causing the protein to change shape The signal is complementary to the receptor protein (like an active site) The signal behaves as a LIGAND: A small molecule that binds to a larger one. This binding can lead to: Change in protein conformation, allowing it to interact w/other cell molecules Aggregation of receptor complexes
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Overview of Cell Signaling
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Most Signal Receptors are Plasma-membrane proteins
3 Types: G-Protein-Linked Receptors Tyrosine-Kinase Receptors Ion-channel receptors
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G-Protein-Linked Receptors
Weaves in and out of the membrane 7 times (has 7 transmembrane domains) Example: Epinephrine receptor The receptor causes a response by interacting with proteins on the cytoplasmic side called G-proteins, cause they bind Guanine nucleotides, GDP, GTP G proteins bound to GDP: Inactive G proteins bound to GTP: Active
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Yo, G (protein) When a ligand binds to a G-Protein-Receptor, the conformation changes and reacts with a G-protein, which causes the GDP to be displaced by GTP, thus activating it. The activated G protein binds to another protein, usually an enzyme, resulting in the activation of a target enzyme. This is temporary, as the G-protein has GTP-ase, which breaks it back down to GDP
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The functioning of a G-Protein
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G-Protein Structure
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Tyrosine-Kinase Receptors
2 Parts: 1. Extracellular ligand-binding domain, 2. cytosolic domain posessing tyrosine-kinase enzyme activity Examples: Growth Factors like PDGFs ( a family of factors which modulate the cell cycle)
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Tyrosine-kinase in action
Ligand binding causes aggregation of 2 receptor units, forming receptor dimers Aggregation activates the tyrosine-kinase activity in cytoplasm These catalyze transfer of phosphate groups from ATP to tyrosine (an amino acid) in a protein. If this protein is part of the cytoplasmic T-K receptor, it’s called autophosphorylation
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More T-K Receptor Action
4. The phosphorylated domain of the receptor reacts w/other proteins, resulting in the activation of another, RELAY protein or proteins. This can jump start MANY transduction systems simultaneously 5. One of the relay proteins may be PROTEIN PHOSPHATASE, which hydrolyzes a Phosphate off of proteins, possibly the tyrosines in the T-K receptors, thus inactivating them. Negative feedback? Yup.
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Tyrosine-Kinase Reception
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ION-Channel Receptors
Some signals bind to ligand-gated ion channels. These are protein pores which open/close due to ligand binding, allowing/blocking the flow of specific ions (Na+, Ca2+) ie.: Neurotransmitters These can be on the plasma membrane OR in the cytoplasm or in the nucleus. The latter are called INTRACELLULAR RECEPTORS, and must be able to pass through the plasma membrane. ie: Steroids, Thyroid hormones, N.O.
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The Structure of an Ion-gated channel
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Signal Transduction Pathways
Pathways relay signals from receptorsCell responses: The ligand signal is not passed directly, but the signal INFORMATION is. At every step the signal is converted or transduced
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Protein Phosphorylation as signal transduction
Caused by protein kinases Very common Commonly found in cytoplasm Don’t act upon themselves (like T-K), but on other proteins, and attach phosphates to serine or threonine residues Some activate, some deactivate target proteins Protein Phosphatases reverse these
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A Phosphorylation Cascade
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Small Molecules/Ions are Important, too.
SECOND MESSENGERS: signal transduction components which are not proteins, but are small water soluble molecules or ions. Two second messenger systems: Cyclic AMP (cAMP) and CA2+-Inositol Triphosphate (IP3) System
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CYCLIC AMP Ligand binds to receptor(1st message)
Receptor conformation changes…G-Protein complex is activated Active G-Protein activates adenyl cyclase (on cytoplasmic side of mem.) Adenyl cyclase converts ATP to cAMP cAMP binds to/activates protein kinase A Protein kinase A phosphorylates various other proteins, leading to a cell response
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CYCLIC AMP
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cAMP as 2nd Messenger
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Ca2+-IP3 Many cells induce a specific response by increasing their cytoplasm’s Ca+ concentration. Ca2+ can be increased by: Ligand binding to Ca2+-gated ion channel Activation of IP3 signaling pathway
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IP. well IP2! Oh Yeah? Well IP3!!!!
ACTIVATION: LigandConformational Chg. In receptor Receptoractivates enzyme phospholipaseThese hydrolyze membrane phospholipidsgive rise to 2nd messengers: IP3 and diacylglycerol DiacylglycerolProtein kinase IP3 binds to Ca2+-gated channels on ER, where CA2+ is stored CA2+signal transduction by affecting target proteins directly OR indirectly by binding indirectly to CALMODULINmodulates Protein kinases and phosphatases
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Maintenance of Ca2+ in Animal cells
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Ca2+ and IP3 in signaling pathways
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Cellular Response Can involve regulation of cytoplasmic activities OR transcription in nucleus
IN CYTOPLASM: Can affect function/activity of proteins which can: Rearrange cytoskeleton Open/close ion channels Serve at key points in matabolic pathways IN NUCLEUS: Signaling system affects synthesis of new proteins/enzymes by modulating gene expression Can regulate transcription(DNAmRNA) factors Dysfunction in these can lead to cancer,etc
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Cytoplasmic response
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Nuclear Response
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Amplification/Specification of Cell Response
AMPLIFICATION: Production of 2nd messengers (cAMP) intrinsically amplify signal. When this is linked to a phosphorylation cascade, the result is almost exponential SIGNAL SPECIFICITY: Only target cells have the appropriate machinery to respond to a given signal (ligand). Different cells can have different signal transduction pathways inside, so 1 signal molecule can affect different cells differently
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Specificity of Cell Signaling
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