NRSC 2100 1st Edition Lecture 12 1 Lipid cascade A Phospholipase C PLC activated by Galpha subunits Gq B PLC activation increases the cleavage of phospholipids part of membranes phosphatidylinositol 4 5 biphosphate into diacyl glycerol DAG and inositol 1 4 5triphosphate IP3 C IP3 then interacts with IP3 receptors on endoplasmic reticulum membrane which opens Ca channels and increases cytosolic Ca Targets of PKC phosphorylation similar to those described for PKA above Enzymes Neurotransmitter receptors Ion channels Structural proteins Transcription factors More usual targets serine and threonine amino acids Long term activation 3 Calcium Ca cascade cytosolic Ca is usually kept very low nanomolar range 10 9 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 M but much higher extracellularly and in organelle reservoirs such as endoplasmic reticulum and mitochondria millimolar range 10 3 M A Cytosolic Ca regulated via 3 Voltage gated Ca channels and other membrane Ca channels e g NMDA 4 IP3 receptor channels in ER 5 3 4 Other cytosolic proteins e g calbindin Calcium Ca cascade B cytosolic Ca activates Calmodulin CALcium MODULated protein C Ca calmodulin Ca calmodulin activates calmodulin dependent protein kinases CaMKII prevalent in neurons Mitogen activated protein kinase MAPK cascades also known as extracellular signalregulated kinases ERKs extensive series of kinases that are activated by phosphorylation by other protein kinases or protein tyrosine kinase receptors through small monomeric Gproteins e g ras family through trk receptors Mediates multiple substrate phosphorylation Some of these include protein phosphatases dephosphorylation PP1 PP2A PP2B best known 5 Nuclear signaling and gene expression messengers such as cAMP and Ca can activate or inhibit transcription factors exemple cAMP response element binding protein CREB regulates gene expression Example cAMP and its modulation of gene expression Divergence One transmitter activates more than one receptor subtype greater postsynaptic response Convergence Different transmitters converge to affect same effector system
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