TY - JOUR
T1 - Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling
AU - Tracy, Christopher M.
AU - Kolesnikov, Alexander V.
AU - Blake, Devon R.
AU - Chen, Ching Kang
AU - Baehr, Wolfgang
AU - Kefalov, Vladimir J.
AU - Willardson, Barry M.
N1 - Publisher Copyright:
© 2015 PLOS ONE.
PY - 2015/2/6
Y1 - 2015/2/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84922569160&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0117129
DO - 10.1371/journal.pone.0117129
M3 - Article
C2 - 25659125
AN - SCOPUS:84922569160
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 2
M1 - e0117129
ER -