An essential role for endocytosis of rhodopsin through interaction of visual arrestin with the AP-2 adaptor.
Previously, we have identified a class of retinal degeneration mutants in Drosophila in which the normally transient interaction between arrestin2 (Arr2) and rhodopsin is stabilized and the complexes are rapidly internalized into the cell body by receptor-mediated endocytosis. The accumulation of protein complexes in the cytoplasm eventually results in photoreceptor cell death. We now show that the endocytic adapter protein AP-2 is essential for rhodopsin endocytosis through an Arr2-AP-2beta interaction, and mutations in Arr2 that disrupt its interaction with the beta subunit of AP-2 prevent endocytosis-induced retinal degeneration. We further demonstrate that if the interaction between Arr2 and AP-2 is blocked, this also results in retinal degeneration in an otherwise wild-type background. This indicates that the Arr2-AP-2 interaction is necessary for the pathology observed in a number of Drosophila visual system mutants, and suggests that regular rhodopsin turnover in wild-type photoreceptor cells by Arr2-mediated endocytosis is essential for photoreceptor cell maintenance.
Orem
Nicholas R
NR
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA.
Xia
Luxi
L
Dolph
Patrick J
PJ
D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000378:metabolism*; D004596:Electroretinography; D004705:Endocytosis / Q000502:physiology*; D008027:Light; D046912:Multiprotein Complexes; D054799:Phospholipase C beta; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000648:ultrastructure; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism
C504666:Arr2 protein, Drosophila; D019390:Arrestins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D050656:Transcription Factor AP-2; D012243:Rhodopsin; D010738:Type C Phospholipases; C468371:NorpA protein, Drosophila; D054799:Phospholipase C beta