Retinal Cone Photoreceptors Require Phosducin-Like Protein 1 for G Protein Complex Assembly and Signaling

作者：Tracy Christopher M; Kolesnikov Alexander V; Blake Devon R; Chen Ching Kang; Baehr Wolfgang; Kefalov Vladimir J^*; Willardson Barry M

来源：PLos One, 2015, 10(2): e0117129.

DOI：10.1371/journal.pone.0117129

G protein beta subunits (G beta) play essential roles in phototransduction as part of G protein beta gamma. (G beta gamma) and regulator of G protein signaling 9 (RGS9)-G beta(5) 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 (G(t2)) and RGS9-G beta(5) 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 G beta gamma and RGS9-G beta(5) assembly in rods and cones, highlighting the importance of PhLP1 and CCT-mediated G beta complex formation in G protein signaling.

• 出版日期2015-2-6