Prolonged G(q) activity triggers fly rhodopsin endocytosis and degradation, and reduces photoreceptor sensitivity.
Rapid deactivation of the Drosophila light receptor rhodopsin, through a visual arrestin Arr2 and a pathway that involves a transcription factor dCAMTA, is required for timely termination of light responses in the photoreceptor neuron. Here we report that this process is also critical for maintenance of the photoreceptor sensitivity. In both dCAMTA- and arr2-mutant flies, the endocytosis of the major rhodopsin Rh1 was dramatically increased, which was mediated by a G(q) protein that signals downstream of rhodopsin in the visual transduction pathway. Consequently, the Rh1 level was downregulated and the photoreceptor became less sensitive to light. Remarkably, the G(q)-stimulated Rh1 endocytosis does not require phospholipase C, a known effector of G(q), but depends on a tetraspanin protein. Our work has identified an arrestin-independent endocytic pathway of G protein-coupled receptor in the fly. This pathway may also function in mammals and mediate an early feedback regulation of receptor signaling.
Han
Junhai
J
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA, USA.
Reddig
Keith
K
Li
Hong-Sheng
HS
D000818:Animals; D030801:Animals, Genetically Modified; D019390:Arrestins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D008027:Light; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
C504665:Arr1 protein, Drosophila; C504666:Arr2 protein, Drosophila; D019390:Arrestins; C522742:CAMTA protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; C502091:Tsp42Ej protein, Drosophila; D012243:Rhodopsin; C468371:NorpA protein, Drosophila; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D034281:Dynamins; C439628:shi protein, Drosophila