N-terminal fatty acylation of transducin profoundly influences its localization and the kinetics of photoresponse in rods

Vasily Kerov, William W. Rubin, Michael Natochin, Nathan A. Melling, Marie E Burns, Nikolai O. Artemyev

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

N-terminal acylation of the α-subunits of heterotrimeric G-proteins is believed to play a major role in regulating the cellular localization and signaling of G-proteins, but physiological evidence has been lacking. To examine the functional significance of N-acylation of a well understood G-protein α-subunit, transducin (Gαt), we generated transgenic mice that expressed a mutant Gαt lacking N-terminal acylation sequence (GαtG2A). Rods expressing GαtG2A showed a severe defect in transducin cellular localization. In contrast to native Gαt , which resides in the outer segments of dark-adapted rods, GαtG2A was found predominantly in the inner compartments of the photoreceptor cells. Remarkably, transgenic rods with the outer segments containing GαtG2A at 5-6%of the Gαt levels in wild-type rods showed only a sixfold reduction in sensitivity and a threefold decrease in the amplification constant. The much smaller than predicted reduction may reflect an increase in the lateral diffusion of transducin and an increased activation rate by photoexcited rhodopsin or more efficient activation of cGMP phosphodiesterase 6 by GαtG2A; alternatively, nonlinear relationships between concentration and the activation rate of transducin also potentially contribute to the mismatch between the amplification constant and quantitative expression analysis of GαtG2A rods. Furthermore, the G2A mutation reduced the GTPase activity of transducin and resulted in two to three times slower than normal recovery of flash responses of transgenic rods, indicating the role of Gαt membrane tethering for its efficient inactivation by the regulator of G-protein signaling 9 GTPase-activating protein complex. Thus, N-acylation is critical for correct compartmentalization of transducin and controls the rate of its deactivation.

Original languageEnglish (US)
Pages (from-to)10270-10277
Number of pages8
JournalJournal of Neuroscience
Volume27
Issue number38
DOIs
StatePublished - Sep 19 2007

Keywords

  • G-proteins
  • N-acylation
  • Phototransduction
  • Retina
  • Transducin
  • Vision

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'N-terminal fatty acylation of transducin profoundly influences its localization and the kinetics of photoresponse in rods'. Together they form a unique fingerprint.

Cite this