JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M611533200 on April 18, 2007

J. Biol. Chem., Vol. 282, Issue 24, 17855-17865, June 15, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
282/24/17855    most recent
M611533200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Houston, C. M.
Right arrow Articles by Smart, T. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Houston, C. M.
Right arrow Articles by Smart, T. G.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Identification of the Sites for CaMK-II-dependent Phosphorylation of GABAA Receptors*

Catriona M. Houston{ddagger}, Henry H. C. Lee{ddagger}§, Alastair M. Hosie{ddagger}, Stephen J. Moss{ddagger}§, and Trevor G. Smart{ddagger}1

From the {ddagger}Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom and the §Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Phosphorylation can affect both the function and trafficking of GABAA receptors with significant consequences for neuronal excitability. Serine/threonine kinases can phosphorylate the intracellular loops between M3-4 of GABAA receptor beta and {gamma} subunits thereby modulating receptor function in heterologous expression systems and in neurons (1, 2). Specifically, CaMK-II has been demonstrated to phosphorylate the M3-4 loop of GABAA receptor subunits expressed as GST fusion proteins (3, 4). It also increases the amplitude of GABAA receptor-mediated currents in a number of neuronal cell types (5-7). To identify which substrate sites CaMK-II might phosphorylate and the consequent functional effects, we expressed recombinant GABAA receptors in NG108-15 cells, which have previously been shown to support CaMK-II modulation of GABAA receptors containing the beta3 subunit (8). We now demonstrate that CaMK-II mediates its effects on {alpha}1beta3 receptors via phosphorylation of Ser383 within the M3-4 domain of the beta subunit. Ablation of beta3 subunit phosphorylation sites for CaMK-II revealed that for {alpha}beta{gamma} receptors, CaMK-II has a residual effect on GABA currents that is not mediated by previously identified sites of CaMK-II phosphorylation. This residual effect is abolished by mutation of tyrosine phosphorylation sites, Tyr365 and Tyr367, on the {gamma}2S subunit, and by the tyrosine kinase inhibitor genistein. These results suggested that CaMK-II is capable of directly phosphorylating GABAA receptors and activating endogenous tyrosine kinases to phosphorylate the {gamma}2 subunit in NG108-15 cells. These findings were confirmed in a neuronal environment by expressing recombinant GABAA receptors in cerebellar granule neurons.


Received for publication, December 18, 2006 , and in revised form, April 17, 2007.

* This work was supported in part by the MRC and the Wellcome Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Pharmacology, UCL, Gower St., London WC1E 6BT, United Kingdom. Tel.: 0044-207-679-2013; E-mail: t.smart{at}ucl.ac.uk.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
J. Physiol.Home page
M. B. Herd, A. R. Haythornthwaite, T. W. Rosahl, K. A. Wafford, G. E. Homanics, J. J. Lambert, and D. Belelli
The expression of GABAA {beta} subunit isoforms in synaptic and extrasynaptic receptor populations of mouse dentate gyrus granule cells
J. Physiol., February 15, 2008; 586(4): 989 - 1004.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.