Functional comparison of RGS9 splice isoforms in a living cell

Two isoforms of the GTPase-activating protein, regulator of G protein signaling 9 (RGS9), control such fundamental functions as vision and behavior. RGS9-1 regulates phototransduction in rods and cones, and RGS9-2 regulates dopamine and opioid signaling in the basal ganglia. To determine their funct...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (52), p.20988-20993
Hauptverfasser: Martemyanov, Kirill A, Krispel, Claudia M, Lishko, Polina V, Burns, Marie E, Arshavsky, Vadim Y
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Sprache:eng
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Zusammenfassung:Two isoforms of the GTPase-activating protein, regulator of G protein signaling 9 (RGS9), control such fundamental functions as vision and behavior. RGS9-1 regulates phototransduction in rods and cones, and RGS9-2 regulates dopamine and opioid signaling in the basal ganglia. To determine their functional differences in the same intact cell, we replaced RGS9-1 with RGS9-2 in mouse rods. Surprisingly, RGS9-2 not only supported normal photoresponse recovery under moderate light conditions but also outperformed RGS9-1 in bright light. This versatility of RGS9-2 results from its ability to inactivate the G protein, transducin, regardless of its effector interactions, whereas RGS9-1 prefers the G protein-effector complex. Such versatility makes RGS9-2 an isoform advantageous for timely signal inactivation across a wide range of stimulus strengths and may explain its predominant representation throughout the nervous system.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0808941106