title: Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole.
abstract: The yeast Rab5 homologue, Vps21p, is known to be involved both in the vacuolar protein sorting (VPS) pathway from the trans-Golgi network to the vacuole, and in the endocytic pathway from the plasma membrane to the vacuole. However, the intracellular location at which these two pathways converge remains unclear. In addition, the endocytic pathway is not completely blocked in yeast cells lacking all Rab5 genes, suggesting the existence of an unidentified route that bypasses the Rab5-dependent endocytic pathway. Here we show that convergence of the endocytic and VPS pathways occurs upstream of the requirement for Vps21p in these pathways. We also identify a previously unidentified endocytic pathway mediated by the AP-3 complex. Importantly, the AP-3-mediated pathway appears mostly intact in Rab5-disrupted cells, and thus works as an alternative route to the vacuole/lysosome. We propose that the endocytic traffic branches into two routes to reach the vacuole: a Rab5-dependent VPS pathway and a Rab5-independent AP-3-mediated pathway.
authors.affiliation: 1] Faculty of Science and Engineering, Waseda University, Wakamatsu-cho, 2-2, Shinjuku-ku, Tokyo 162-8480, Japan [2] Research Center for RNA Science, RIST, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Junko Y
authors.initials: JY
authors.lastname: Toshima
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Show
authors.initials: S
authors.lastname: Nishinoaki
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yamamoto
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Furukawa
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1 A-3400 Klosterneuburg, Austria.
authors.forename: Daria Elisabeth
authors.initials: DE
authors.lastname: Siekhaus
authors.affiliation: Department of Anatomy, University of Miyazaki Faculty of Medicine, Miyazaki 889-1692, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaguchi
authors.affiliation: 1] Research Center for RNA Science, RIST, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan [2] Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Toshima
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D033963:Adaptor Protein Complex 3; D029701:Saccharomyces cerevisiae Proteins; C086866:VPS21 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins