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Signal Transduction

B cell becomes r7 neuron when signal detected a b r7

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B cell becomes R7 neuron when signal detected A B R7 A B cone Signal Target Perform genetic screen for loss of cellular output that resembles loss of signaling cell B cell becomes cone cell instead of R7 neuron Loss of signal can be from mutation in ligand, receptor, or intracellular effectors A X Selective killing of A cell results in B cell becoming a cone cell instead of R7 neuron A cell sends signal to B cell to become R7 neuron 13 B R7 B cone
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A Mutant Ligand B Wild type ligand B Wild type receptor A Mutant Receptor Perform mutant clonal analysis to determine cellular autonomy of the effects Ex. If A cell is mutant and B cell is wild type, what phenotype do you see? If mutation is in receptor, then the B cell will become R7 neuron. If mutation is in ligand, then the B cell will become cone cell. Which cell is the signaling cell and which one is the target? Clonal Analysis Allows for Determination of Cellular Autonomy 14 Green=wild type Pink=mutant
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GPCR signaling in different tissues can elicit different responses epinephrine Increase in cAMP levels Glycogen breakdown Glucose release Increase in intracellular Ca++ Muscle Contraction 15
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G-protein coupled receptors 7-pass transmembrane receptors N-term extracellular C-term cytoplasmic Associate with trimeric G-proteins Act as GEF for G-protein Lead to increases in second messengers cAMP Ca++ Effector molecules found in membrane 16
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Trimeric G-protein Composed of 3 subunits: α , β , and γ α contains GTPase activity α and γ tethered to plasma membrane via lipid tails When α bound to GDP, also interacts with β and γ ±± > This is the off position When GPCR activated, binds to G- protein and acts as a GEF Stimulates exchange of GDP for GTP in the α subunit 17
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Second Messengers Small intracellular molecules cAMP Ca++ Easily diffusable--> reach locations distant from PM Amplify signal 100-1000 fold
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B cell becomes R7 neuron when signal detected A B R7 A B...

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