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

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

doi:10.1371/journal.pone.0117129

Christopher M Tracy, Devon R Blake + Show 6 more

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https://doi.org/10.1371/journal.pone.0117129

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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.

Highlights

The rod and cone photoreceptor cells of the retina mediate vertebrate vision
phosducin-like protein 1 (PhLP1) deletion caused a striking loss of both G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-G protein β5 subunit (Gβ5) in rods, resulting in reduced sensitivity, decreased amplification rate and prolonged recovery time in rod photoresponses. These findings demonstrated that PhLP1 is required for Gβγ and RGS9-Gβ5 assembly in rods and suggested that this mechanism could be shared in other cell types
We found that PhLP1 deletion caused a marked reduction in expression of Gt2 and RGS9-Gβ5 complexes in cones, which resulted in a major disruption of cone photoresponses

Summary

Introduction

The rod and cone photoreceptor cells of the retina mediate vertebrate vision. These cell types are designed for light detection under different conditions. Rods are high-sensitivity sensors capable of detecting single photons, while cones are lower-sensitivity sensors with a broader dynamic range and faster response kinetics [1]. The two cell types express different visual pigments, with rods expressing rhodopsin and cones expressing up to three distinct cone opsins.

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