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Molecular and Cellular Biology, June 2009, p. 3033-3044, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.01449-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Changes in Striatal Signaling Induce Remodeling of RGS Complexes Containing Gβ5 and R7BP Subunits{triangledown}

Garret R. Anderson,1 Rafael Lujan,2 and Kirill A. Martemyanov1*

Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455,1 Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, 02006 Albacete, Spain2

Received 15 September 2008/ Returned for modification 8 December 2008/ Accepted 9 March 2009

Neurotransmitter signaling via G protein coupled receptors is crucially controlled by regulators of G protein signaling (RGS) proteins that shape the duration and extent of the cellular response. In the striatum, members of the R7 family of RGS proteins modulate signaling via D2 dopamine and µ-opioid receptors controlling reward processing and locomotor coordination. Recent findings have established that R7 RGS proteins function as macromolecular complexes with two subunits: type 5 G protein β (Gβ5) and R7 binding protein (R7BP). In this study, we report that the subunit compositions of these complexes in striatum undergo remodeling upon changes in neuronal activity. We found that under normal conditions two equally abundant striatal R7 RGS proteins, RGS9-2 and RGS7, are unequally coupled to the R7BP subunit, which is present in complex predominantly with RGS9-2 rather than with RGS7. Changes in the neuronal excitability or oxygenation status resulting in extracellular calcium entry, uncouples RGS9-2 from R7BP, triggering its selective degradation. Concurrently, released R7BP binds to mainly intracellular RGS7 and recruits it to the plasma membrane and the postsynaptic density. These observations introduce activity-dependent remodeling of R7 RGS complexes as a new molecular plasticity mechanism in striatal neurons and suggest a general model for achieving rapid posttranslational subunit rearrangement in multisubunit complexes.


* Corresponding author. Mailing address: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St., SE, Minneapolis, MN 55455. Phone: (612) 626-5309. Fax: (612) 625-8408. E-mail: martemyanov{at}umn.edu

{triangledown} Published ahead of print on 30 March 2009.


Molecular and Cellular Biology, June 2009, p. 3033-3044, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.01449-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.