In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 19, No. 21 ( 1999-11-01), p. 9228-9234
Abstract:
GABA receptors (GABA A ) are the major sites of fast synaptic inhibition in the brain and can be assembled from five subunit classes: α, β, γ, δ, and ε. Receptor function can be regulated by direct phosphorylation of β and γ2 subunits, but how kinases are targeted to GABA A receptors is unknown. Here we show that protein kinase C-βII (PKC-βII) is capable of directly binding to the intracellular domain of the receptor β1 and β3 subunits, but not to those of the α1 or γ2 subunits. Moreover, associating PKC-βII is capable of specifically phosphorylating serine 409 in β1 subunit and serines 408/409 within the β3 subunit, key residues for modulating GABA A receptor function. The receptor for activated C kinase (RACK-1) was found also to bind to the β1 subunit intracellular domain, but PKC binding appeared to be independent of this protein. Using immunoprecipitation, the association of PKC isoforms and RACK-1 with neuronal GABA A receptors was seen. Furthermore, PKC isoforms associating with neuronal receptors were capable of phosphorylating the receptor β3 subunit. Together, these observations suggest GABA A receptors are intimately associated with PKC isoforms via a direct interaction with receptor β subunits. This interaction may serve to localize PKC activity to GABA A receptors in neurons allowing the rapid regulation of receptor activity by cell-signaling pathways that modify PKC activity.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.19-21-09228.1999
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
1999
detail.hit.zdb_id:
1475274-8
SSG:
12
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