Interaction of retinal guanylate cyclase with the α subunit of transducin: Potential role in transducin localization

Derek H. Rosenweig, Saidas K. Nair, Konstantin Levay, Igor Peshenko, John W. Crabb, Alexander M. Dizhoor, Vladlen Z. Slepak

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Vertebrate phototransduction is mediated by cGMP, which is generated by retGC (retinal guanylate cyclase) and degraded by cGMP phosphodiesterase. Light stimulates cGMP hydrolysis via the G-protein transducin, which directly binds to and activates phosphodiesterase. Bright light also causes relocalization of transducin from the OS (outer segments) of the rod cells to the inner compartments. In the present study, we show experimental evidence for a previously unknown interaction between Gαt (the transducin α subunit) and retGC. Gαt co-immunoprecipitates with retGC from the retina or from co-transfected COS-7 cells. The retGC-Gαt complex is also present in cones. The interaction also occurs in mice lacking RGS9 (regulator of G-protein signalling 9), a protein previously shown to associate with bothGαt and retGC. The Gαt-retGC interaction is mediated primarily by the kinase homology domain of retGC, which binds GDP-bound Gαt stronger than the GTP[S] (GTPγS; guanosine 5′-[γ-thio]triphosphate) form. Neither Gαt nor Gβγ. affect retGC-mediated cGMP synthesis, regardless of the presence of GCAP (guanylate cyclase activating protein) and Ca2+. The rate of light-dependent transducin redistribution from the OS to the inner segments is markedly accelerated in the retGC-1-knockout mice, while the migration of transducin to the OS after the onset of darkness is delayed. Supplementation of permeabilized photoreceptors with cGMP does not affect transducin translocation. Taken together, these results suggest that the protein-protein interaction between Gαt and retGC represents a novel mechanism regulating light-dependent translocation of transducin in rod photoreceptors.

Original languageEnglish (US)
Pages (from-to)803-812
Number of pages10
JournalBiochemical Journal
Volume417
Issue number3
DOIs
StatePublished - Feb 1 2009

Keywords

  • CGMP
  • G-protein
  • Photoreceptor
  • Subcellular localization

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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