title: Involvement of Rabphilin3 in endocytosis through interaction with Rabaptin5.
abstract: Rabphilin3 and rabaptin5 are downstream target molecules of the Rab3 and -5 subfamily small G proteins that are implicated in exocytosis and endocytosis, respectively. We examined here the physical and functional relationship between the Rab3-rabphilin3 and Rab5-rabaptin5 systems. Rabphilin3 interacted with rabaptin5 at the N-terminal region (amino acids 1-280), which GTP-Rab3A interacted with. The interaction of rabphilin3 with rabaptin5 was inhibited by guanosine 5'-(3-O-thio)triphosphate-Rab3A. Overexpression of the N-terminal fragment of rabphilin3 (amino acids 1-280) inhibited the receptor-mediated endocytosis of transferrin, and this inhibition was overcome by co-transfection with a dominant active mutant of Rab3A or rabaptin5 in PC12 and HeLa cells. These results suggest that rabphilin3, free of GTP-Rab3A, regulates endocytosis through interaction with rabaptin5 after rabphilin3 complexed with GTP-Rab3A regulates exocytosis.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita 565, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohya
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Takai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002417:Cattle; D002460:Cell Line; D004705:Endocytosis; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D018411:Spodoptera; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000097624:Rabphilin-3A
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019204:GTP-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000097624:Rabphilin-3A