Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling

Christopher M. Tracy, Alexander V. Kolesnikov, Devon R. Blake, Ching Kang Chen, Wolfgang Baehr, Vladimir J. Kefalov, Barry M. Willardson

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

G protein β subunits (Gβ) play essential roles in phototransduction as part of G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-Gβ5 heterodimers. Both are obligate dimers that rely on the cytosolic chaperone CCT and its co-chaperone PhLP1 to form complexes from their nascent polypeptides. The importance of PhLP1 in the assembly process was recently demonstrated in vivo in a retinal rod-specific deletion of the PhLP1 gene. To test whether this is a general mechanism that also applies to other cell types, we disrupted the PhLP1 gene specifically in mouse cones and measured the effects on G protein expression and cone visual signal transduction. In PhLP1-deficient cones, expression of cone transducin (Gt2) and RGS9-Gβ5 subunits was dramatically reduced, resulting in a 27-fold decrease in sensitivity and a 38-fold delay in cone photoresponse recovery. These results demonstrate the essential role of PhLP1 in cone G protein complex formation. Our findings reveal a common mechanism of Gβγ and RGS9-Gβ5 assembly in rods and cones, highlighting the importance of PhLP1 and CCT-mediated Gβ complex formation in G protein signaling.

Original languageEnglish
Article numbere0117129
JournalPloS one
Volume10
Issue number2
DOIs
StatePublished - Feb 6 2015

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    Tracy, C. M., Kolesnikov, A. V., Blake, D. R., Chen, C. K., Baehr, W., Kefalov, V. J., & Willardson, B. M. (2015). Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. PloS one, 10(2), [e0117129]. https://doi.org/10.1371/journal.pone.0117129