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Transcript
Cell Communication Chapter 11 p. 201-217 Evolution of Cell Signaling • There is great similarity in cell-signaling mechanisms of yeasts & mammals ▫ Suggests the processes evolved very long ago • Signal Transduction Pathway: process by which a signal on cell’s surface is converted into specific cellular response Local & Long-Distance Signaling • Some cells communicate thru direct contact w/ one another (i.e. plasmosdesmata) • Local Regulators: message travels only short distance ▫ Paracrine Signaling: local regulator secretes message into extracellular fluid many neighboring cells ▫ Synaptic Signaling: neurotransmitters released into synapse (space between 2 cells) one target cell • Long-Distance Signaling: uses hormones, released into vessels, to carry signal throughout body to target ▫ Animals: endocrine signaling ▫ Plants: growth regulators 3 Stages of Cell Signaling: a preview • 1) Reception: how target cell detects signal on membrane surface or inside cell • 2) Transduction: bound signal causes changes that bring about a cellular response ▫ “Signal Transduction Pathway” • 3) Response: can be almost anything ▫ i.e. catalysts, gene activation, etc Reception: an overview • Signals will only be “heard” by cells w/ specific receptor proteins ▫ Signal molecule is complimentary in shape to receptor ▫ Ligand: any molecule that specifically binds to another (larger) molecule Usually causes receptor protein to change shape Intracellular Receptors • Located in cytoplasm or nucleus, instead of plasma membrane • Signal must pass through cytoplasm of receptor cell (must be small, hydrophobic) ▫ Testosterone: binds to receptor protein in cytoplasm, both enter nucleus & “turn on” genes for male sex characteristics Plasma Membrane Receptors • H2O-soluble signals bind to receptors embedded in plasma membrane ▫ Receptor then transmits info inside cell by changing shape or aggregating (combining w/ 1+ other receptor proteins) • 3 Types: ▫ G-protein-linked receptors ▫ Receptor tyrosine kinases ▫ Ion channel receptors G-Protein-Linked Receptors • Utilizes G protein (guanosine) to carry signal from receptor enzyme further down in membrane ▫ Activated enzyme triggers a cell response • Consists of single polypeptide w/ 7 α helices • Play role in: embryonic devlpmnt, vision, cholera, botulism ▫ 60% modern medicines influence G-protein pathways Receptor Tyrosine Kinases • Trigger more than 1 signal transduction pathway at once ▫ Each may activate 10+ pathways & responses ▫ Help regulate & coordinate cell growth & reproduction • Kinase: an enzyme that catalyzes the transfer of phosphate groups (from ATP tyrosine) • Some abnormal RTK’s can function w/out a signal, leading to cancer Ion Channel Receptors • Ligand-Gated Ion Channel: contains a “gated” region that allows or blocks ions from entering cell (Na+, Ca2+) ▫ When signal (ligand) binds, gate opens & ions enter ▫ When ligand absent, gate is closed ▫ Play role in nervous system (neurotransmitters act as ligands) • Voltage-Gated Ion Channels: controlled by electrical signals instead of ligands Transduction: an overview • Usually a multi-step process to bring signal from receptor (on membrane) to target molecule (inside cell) ▫ Signal may become amplified by activating multiple molecules 1 signal large response; helps coordinate & regulate processes ▫ Signal itself is not relayed, but information is (conformational changes in proteins) Protein Phosphorylation & Dephosphorylation • Protein Kinase “on”: enzyme that transfers a phosphate group from ATP a protein ▫ Usually serine or threonine (amino acids) ▫ Every time a phosphate is added to the next protein, causes a conformational change (“activates” the protein) ▫ Regulates proteins involved in cell reproduction (mitosis & meiosis) ▫ Abnormal protein kinases may cause abnormal cell growth cancer • Protein Phosphatases “off”: enzyme that removes a phosphate from proteins (“dephosphorylation”) ▫ Deactivates protein & turns off signal transduction pathway ▫ Makes protein kinases available to do more work Second Messengers • Second Messenger: small, non-protein, H2O soluble molecules or ions involved in signal transduction pathways ▫ Readily spread through cell by diffusion ▫ Used with G-protein-linked receptors & RTK’s ▫ 2 Types: Cyclic AMP (cAMP) Ca2+ Ions & IP3 Cyclic AMP • Involved in breakdown of glycogen glucose in liver cells when epinephrine (signal) binds to Gprotein-linked receptor ▫ Adenylyl Cyclase: converts ATP cAMP when signal binds ▫ Many cAMP made (signal is amplified) & signal is broadcasted throughout cytoplasm ▫ cAMP activates protein kinase A, which phosphorylates other proteins In cholera, bacteria modifies G protein so stays active & keeps stimulating production of cAMP In Viagra, cGMP (cousin of cAMP) is inhibited, resulting in dilation of blood vessels Ca2+ Ions & IP3 • Involved in animal muscle contraction, secretion, cell division and in plant greening • Used in G-protein-linked and RTK pathways • Ca2+ ions constantly pumped out of cytosol into ECF, ER, mitochondria, & chloroplasts ▫ [Ca2+] in cytosol ▫ [Ca2+] in ECF, ER, mitochondria, & chloroplast • Signal IP3 (or DAG) stimulates release of Ca2+ from ER activation of proteins response Response • Cytoplasmic Responses: opening/closing of ion channels in membrane, or change in cell metabolism ▫ i.e.: epinephrine signals results in activation of enzyme that catalyzes glycogen breakdown • Nuclear Responses: genes may be turned on/off that affect protein synthesis ▫ i.e. growth factor signal results in synthesis of mRNA which will result in protein Regulation of Response • Signal Amplification: one signal causes large response • Specificity: different cells have different proteins ▫ i.e. signal, relay, & response proteins • Efficiency: proteins are too large to diffuse through cytoplasm; relay would be inefficient ▫ Scaffolding Proteins: hold many relay molecules in same place to increase efficiency • Termination: signal molecules bind reversibly ▫ When absent, receptor & relay molecules inactive & able to do more work