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 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.
Martemyanov
Kirill A
KA
Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Krispel
Claudia M
CM
Lishko
Polina V
PV
Burns
Marie E
ME
Arshavsky
Vadim Y
VY
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D015293:Transducin / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
D020033:Protein Isoforms; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D015293:Transducin