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The Journal of Neuroscience, February 1, 1998, 18(3):905-913
RGS4 Inhibits Signaling by Group I Metabotropic Glutamate
Receptors
Julie A.
Saugstad,
Michael J.
Marino,
Julie A.
Folk,
John R.
Hepler, and
P. Jeffrey
Conn
Department of Pharmacology, Emory University, Atlanta, Georgia
30322
Metabotropic glutamate receptors (mGluRs) couple to heterotrimeric
G-proteins and regulate cell excitability and synaptic transmission in
the CNS. Considerable effort has been focused on understanding the
cellular and biochemical mechanisms that underlie regulation of
signaling by G-proteins and their linked receptors, including the
mGluRs. Recent findings demonstrate that regulators of G-protein
signaling (RGS) proteins act as effector antagonists and
GTPase-activating proteins for G subunits to inhibit
cellular responses by G-protein-coupled receptors. RGS4 blocks
Gq activation of phospholipase C and is expressed broadly in rat brain. The group I mGluRs (mGluRs 1 and 5) couple to
Gq pathways to regulate several effectors in the CNS. We
examined the capacity of RGS4 to regulate group I mGluR responses. In
Xenopus oocytes, purified RGS4 virtually abolishes the
mGluR1a- and mGluR5a-mediated but not the inositol
trisphospate-mediated activation of a calcium-dependent chloride
current. Additionally, RGS4 markedly attenuates the mGluR5-mediated inhibition of potassium currents in hippocampal CA1 neurons. This inhibition is dose-dependent and occurs at concentrations that are
virtually identical to those required for inhibition of phospholipase C
activity in NG108-15 membranes and reconstituted systems using purified proteins. These findings demonstrate that RGS4 can modulate mGluR responses in neurons, and they highlight a previously unknown mechanism for regulation of G-protein-coupled receptor signaling in the
CNS.
Key words:
RGS4; RGS proteins; metabotropic glutamate receptor; hippocampus; G-proteins; synaptic regulation; Xenopus
Copyright © 1998 Society for Neuroscience 0270-6474/98/183905-09$05.00/0
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|
|
|
|
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