RGS9 concentration matters in rod phototransduction

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36 Scopus citations

Abstract

The transduction of light by retinal rods and cones is effected by homologous G-protein cascades whose rates of activation and deactivation determine the sensitivity and temporal resolution of photoreceptor signaling. In mouse rods, the ratelimiting step of deactivation is hydrolysis of GTP by the G-protein-effector complex, catalyzed by the RGS9 complex. Here, we incorporate a "Michaelis module" describing the RGS9 reaction into the conventional scheme for phototransduction and show that this augmented scheme can account precisely for the dominant recovery rate of intact rods in which RGS9 expression varies over a 20-fold range. Furthermore, by screening the parameter space of the scheme with maximum-likelihood methodology, we tested specific hypotheses about the rate constant for rhodopsin deactivation, and about the forward, reverse, and catalytic constants for RGS9-mediated G-protein deactivation. These tests reliably exclude lifetimes >∼50 ms for rhodopsin, and reveal that the dominant time constant of rod photoresponse recovery is 1/(Vmax/Km) for the RGS9 reaction, with k cat/Km ≈ 0.04 μm2 s-1 and kcat > 35 s-1 (or Km > 840 μm -2). All together, the new kinetic scheme and analysis explain how and why RGS9 concentration matters in rod phototransduction, and they provide a framework for understanding the molecular mechanisms that ratelimit deactivation in other G-protein systems.

Original languageEnglish (US)
Pages (from-to)1538-1547
Number of pages10
JournalBiophysical Journal
Volume97
Issue number6
DOIs
StatePublished - Sep 16 2009

ASJC Scopus subject areas

  • Biophysics

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