Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor

Masumi Eto, Roland Bock, David L. Brautigan, David J Linden

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)1145-1158
Number of pages14
JournalNeuron
Volume36
Issue number6
DOIs
StatePublished - Dec 19 2002

Fingerprint

Long-Term Synaptic Depression
Myosin-Light-Chain Phosphatase
Physiological Phenomena
AMPA Receptors
Gene Silencing
Muscle Contraction
G-Protein-Coupled Receptors
Neutralizing Antibodies
Vascular Smooth Muscle
Small Interfering RNA
Blood Vessels
Glutamic Acid
Down-Regulation
Phosphorylation
moesin
cyclopropapyrroloindole
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor. / Eto, Masumi; Bock, Roland; Brautigan, David L.; Linden, David J.

In: Neuron, Vol. 36, No. 6, 19.12.2002, p. 1145-1158.

Research output: Contribution to journalArticle

@article{1847c9778be24a6f957d3d94232f1113,
title = "Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor",
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 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.",
author = "Masumi Eto and Roland Bock and Brautigan, {David L.} and Linden, {David J}",
year = "2002",
month = "12",
day = "19",
doi = "10.1016/S0896-6273(02)01107-8",
language = "English (US)",
volume = "36",
pages = "1145--1158",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=0037137711&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037137711&partnerID=8YFLogxK

U2 - 10.1016/S0896-6273(02)01107-8

DO - 10.1016/S0896-6273(02)01107-8

M3 - Article

C2 - 12495628

AN - SCOPUS:0037137711

VL - 36

SP - 1145

EP - 1158

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 6

ER -