Regulation of the rhodopsin protein phosphatase, RDGC, through interaction with calmodulin.
Hundreds of G protein-coupled receptors (GPCRs) and at least six GPCR kinases have been identified, but the only GPCR phosphatase that has been definitively demonstrated is the rhodopsin phosphatase encoded by the rdgC locus of Drosophila. Mutations in rdgC result in defects in termination of the light response and cause severe retinal degeneration. In the current work, we demonstrate that RDGC binds to calmodulin, and a mutation in an IQ motif that eliminates the calmodulin/RDGC interaction prevents dephosphorylation of rhodopsin in vivo and disrupts termination of the photoresponse. Our data indicate that RDGC is a novel calmodulin-dependent protein phosphatase and raise the possibility that regulation of other GPCRs through dephosphorylation may be controlled by calmodulin-dependent protein phosphatases related to RDGC.
Lee
S J
SJ
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Montell
C
C
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D002147:Calmodulin / Q000378:metabolism*; D020134:Catalytic Domain; D004330:Drosophila; D029721:Drosophila Proteins; D004596:Electroretinography; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010775:Photic Stimulation; D017956:Photoreceptor Cells, Invertebrate / Q000201:enzymology; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology; D012243:Rhodopsin / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D029721:Drosophila Proteins; D012243:Rhodopsin; C107424:PPEF1 protein, human; D010749:Phosphoprotein Phosphatases; C074643:rdgC protein, Drosophila; D019204:GTP-Binding Proteins