The fly CAMTA transcription factor potentiates deactivation of rhodopsin, a G protein-coupled light receptor.
Control of membrane-receptor activity is required not only for the accuracy of sensory responses, but also to protect cells from excitotoxicity. Here we report the isolation of two noncomplementary fly mutants with slow termination of photoresponses. Genetic and electrophysiological analyses of the mutants revealed a defect in the deactivation of rhodopsin, a visual G protein-coupled receptor (GPCR). The mutant gene was identified as the calmodulin-binding transcription activator (dCAMTA). The known rhodopsin regulator Arr2 does not mediate this visual function of dCAMTA. A genome-wide screen identified five dCAMTA target genes. Of these, overexpression of the F box gene dFbxl4 rescued the mutant phenotypes. We further showed that dCAMTA is stimulated in vivo through interaction with the Ca(2+) sensor calmodulin. Our data suggest that calmodulin/CAMTA/Fbxl4 may mediate a long-term feedback regulation of the activity of Ca(2+)-stimulating GPCRs, which could prevent cell damage due to extra Ca(2+) influx.
Han
Junhai
J
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Gong
Ping
P
Reddig
Keith
K
Mitra
Mirna
M
Guo
Peiyi
P
Li
Hong-Sheng
HS
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D001483:Base Sequence; D002147:Calmodulin / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology
C504666:Arr2 protein, Drosophila; D019390:Arrestins; D002147:Calmodulin; D029721:Drosophila Proteins; D044783:F-Box Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D012243:Rhodopsin