Retinal Cone Photoreceptors Require Phosducin-Like Protein 1 for G Protein Complex Assembly and Signaling
Year: 2015
Type: article
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.
Source: PLoS ONE
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1997427537, Recovery of Phototransduction, G2753724968, G2765546596, Photoreceptor Ciliopathies: UNC119 Paralogs and NPHP10/NPHP5, MECHANISMS OF ADAPTATION IN MAMMALIAN CONES, G4011959277, Recovery of Phototransduction, G5208600249, G545253499, G590436315, Membrane Protein Transport in Photoreceptors, G6000982847, Pharmacological Treatment of Retinal Diseases, G7217857936, G8394839864, Structural basis for chaperone-dependent folding of beta-propeller proteins essential for vision, G9000161448, G9000264003, University of Utah Core Vision Research Grant
OpenAlex ID: W2008335425