Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors

Chun Wan J. Lai, Alexander V. Kolesnikov, Jeanne M. Frederick, Devon R. Blake, Li Jiang, Jubal S. Stewart, Ching Kang Chen, Jeffery R. Barrow, Wolfgang Baehr, Vladimir J. Kefalov, Barry M. Willardson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

G-protein β subunits perform essential neuronal functions as part of G-protein βγ and Gβ5-regulators of G-protein signaling (RGS) complexes. Both Gβγ and Gβ5-RGS are obligate dimers that are thought to require the assistance of the cytosolic chaperonin CCT and a cochaperone, phosducin-like protein 1 (PhLP1) for dimer formation. To test this hypothesis in vivo, we deleted the Phlp1 gene in mouse (Mus musculus) retinal rod photoreceptor cells and measured the effects on G-protein biogenesis and visual signal transduction. In the PhLP1-depleted rods, Gβγ dimer formation was decreased 50-fold, resulting in a >10-fold decrease in light sensitivity. Moreover, a 20-fold reduction in Gβ5 and RGS9-1 expression was also observed, causing a 15-fold delay in the shutoff of light responses. These findings conclusively demonstrate in vivo that PhLP1 is required for the folding and assembly of both Gβγ and Gβ5-RGS9.

Original languageEnglish
Pages (from-to)7941-7951
Number of pages11
JournalJournal of Neuroscience
Volume33
Issue number18
DOIs
StatePublished - 2013

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