Arrestin effects on internalization of vasopressin receptors.
Arrestins have been shown to facilitate the recruitment of G protein-coupled receptors to the clathrin-coated vesicles that mediate their internalization. After (8)Arg-vasopressin-induced internalization, the human V2 vasopressin receptor failed to recycle to the cell surface, whereas the vasopressin type 1a receptor (V1a) subtype did. The possibility that the lack of recycling could identify a novel role for arrestins was investigated by examining the effect of coexpressing wild-type and dominant negative arrestins on the recycling of wild-type and mutant V2 and V1a receptors. Coexpression of the V1a or V2 receptors with the last 100 amino acids of arrestin reduced significantly their internalization, whereas coexpression of wild-type and mutant arrestins had diverse effects on internalization. Arrestin3 but not arrestin2 increased the internalization of the V1aR without altering its recycling pattern. Both nonvisual arrestins enhanced vasopressin type 2 receptor (V2R) internalization, inducing the appearance of a pool of recycling receptor in addition to the nonrecycling pool. The effect of arrestins on the internalization of the chimeric V1a/V2 receptor and its reciprocal chimera was specified by the identity of the carboxyl-terminal segment. The S363A mutation that confers recycling to the V2R did not alter its interaction with arrestins. Truncation of the carboxyl-terminal segment of the V2R impaired ligand-induced internalization that could be fully restored by wild-type arrestins. Internalization of the V2 and V1a receptors required dynamin GTPase activity.
Bowen-Pidgeon
D
D
Department of Anesthesiology, University of California Los Angeles School of Medicine, Los Angeles, CA 90095-7115.
Innamorati
G
G
Sadeghi
H M
HM
Birnbaumer
M
M
D019393:Arrestin / Q000494:pharmacology*; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects*; D017353:Gene Deletion; D006801:Humans; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D019393:Arrestin; D017483:Receptors, Vasopressin; D011993:Recombinant Fusion Proteins