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CU-Boulder NRSC 2100 - Intracellular Signaling

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NRSC 2100 1st Edition Lecture 11 1 1 2 3 Intracellular signaling the all important sibling of membrane potential signaling a Second messenger systems b Effector pathways Essential components of Signaling Systems A molecular signal A receptor molecule A target effector molecule response Often involves cascades the neurotransmitter glutamate signal Acts on glutamate receptor protein receptor Opens an ionic membrane channel target effector 1 Molecular signals Cell impermeant molecules includes neurotransmitters do not readily cross membranes These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute 2 3 1 2 3 4 Cell permeant molecules includes steroidbased molecules thyroid hormone thyroxins and retinoids related to vitamin A Cell associated molecules cell membrane proteins to cell membrane receptor interactions of closely apposed cells Receptor molecules Channel linked receptors ionotropic Metabotropic receptors G protein coupled receptors Enzyme linked receptors Intracellular receptors Target Effector Cascades G proteins and their targets both heteromeric alpha beta gamma small proteins and monomeric small G proteins forms generally activate enzymes that regulate the production of secondmessengers 5 Second messenger targets second messengers regulates several target enzymes e g PKA 6 Nuclear messenger targets protein modification induced in transcription factor targets can translocate to nucleus and modify gene transcription CREB Major G proteins targets 1 Cyclic nucleotide cascades A Adenylyl cyclase is targeted by several types of activated alpha subunits GTP leading to increases alpha stimulatory or Gs or decreases alpha inhibitory or Gi in cAMP i B C Guanylyl cyclase similar for cGMP i cAMP cGMP cascades cAMP cGMP regulates the cAMP cGMP dependent protein kinases PKA and PKG respectively Kinases and Phosphatases the Yin and Yang Phosphorylation and Dephosphorylation Phosphate groups added to or removed from a protein Changes conformation and biological activity The Function of Signal Cascades Signal amplification by GPCRs Cyclic nucleotide cascades Phosphorylation Targets of PKA and PKG Enzymes Neurotransmitter receptors Ion channels Structural proteins Transcription factors CREB More usual targets serine and threonine amino acids Thousands of protein targets even in neurons


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