Functional comparison of RGS9 splice isoforms in a living cell

Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20988-93. doi: 10.1073/pnas.0808941106. Epub 2008 Dec 19.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / physiology
  • Animals
  • Basal Ganglia / metabolism
  • Behavior, Animal / physiology
  • Mice
  • Mice, Transgenic
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Transducin / metabolism
  • Vision, Ocular / physiology*

Substances

  • Protein Isoforms
  • RGS Proteins
  • regulator of g-protein signaling 9
  • Transducin