Abstract
Cerebellar LTD requires brief activation of PKC and is expressed as a functional downregulation of AMPA receptors. Modulation of vascular smooth-muscle contraction by G protein-coupled receptors (called Ca(2+) sensitization) also involves PKC phosphorylation and activation of a specific inhibitor of myosin/moesin phosphatase (MMP). This inhibitor, called CPI-17, is also expressed in brain. Here, we tested the hypothesis that LTD, like Ca(2+) sensitization, employs a PKC/CPI-17 cascade. Introduction of activated recombinant CPI-17 into cells produced a use-dependent attenuation of glutamate-evoked responses and occluded subsequent LTD. Moreover, the requirement for endogenous CPI-17 in LTD was demonstrated with neutralizing antibodies plus gene silencing by siRNA. These interventions had no effect on basal synaptic strength but blocked LTD induction. Thus, a biochemical circuit that involves PKC-mediated activation of CPI-17 modulates the distinct physiological processes of vascular contractility and cerebellar LTD.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies / pharmacology
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Cells, Cultured
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Cerebellar Cortex / cytology
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Cerebellar Cortex / drug effects
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Cerebellar Cortex / enzymology*
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Enzyme Inhibitors / pharmacology
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Fetus
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Glutamic Acid / pharmacology
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Immunohistochemistry
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Intracellular Signaling Peptides and Proteins
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology*
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Mice
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Muscle Proteins / antagonists & inhibitors
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Myosin-Light-Chain Phosphatase
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Neurons / cytology
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Neurons / drug effects
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Neurons / enzymology*
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / metabolism*
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Phosphoproteins / antagonists & inhibitors
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Kinase C / metabolism*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Synapses / drug effects
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Synapses / enzymology*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Antibodies
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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Muscle Proteins
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Phosphoproteins
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Ppp1r14a protein, mouse
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RNA, Small Interfering
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Glutamic Acid
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Protein Kinase C
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Phosphoprotein Phosphatases
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Myosin-Light-Chain Phosphatase