TY - JOUR
T1 - Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor
AU - Eto, Masumi
AU - Bock, Roland
AU - Brautigan, David L.
AU - Linden, David J.
N1 - Funding Information:
Thanks to Sandra Rossie for providing constitutively active and point mutant inactive PP5 and to Hee Jung Chung and members of the Linden lab for helpful comments. This work was supported by USPHS MH51106 (D.J.L.), MH01590 (D.J.L.), CA40024 (D.L.B.), GM56362 (D.L.B.), the Develbiss Fund (D.J.L.), and a fellowship from the American Heart Association (M.E.).
PY - 2002/12/19
Y1 - 2002/12/19
N2 - 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 Ca2+ 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 Ca2+ 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.
AB - 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 Ca2+ 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 Ca2+ 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.
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U2 - 10.1016/S0896-6273(02)01107-8
DO - 10.1016/S0896-6273(02)01107-8
M3 - Article
C2 - 12495628
AN - SCOPUS:0037137711
SN - 0896-6273
VL - 36
SP - 1145
EP - 1158
JO - Neuron
JF - Neuron
IS - 6
ER -