Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole Journal Article

Author(s): Toshima, Junko Y; Nishinoaki, Show; Sato, Yoshifumi; Yamamoto, Wataru; Furukawa, Daiki; Siekhaus, Daria E; Sawaguchi, Akira; Toshima, Jiro
Article Title: Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole
Affiliation IST Austria
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.
Journal Title: Nature Communications
Volume: 5
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2014-03-25
Start Page: Article number: 3498
DOI: 10.1038/ncomms4498
Notes: We thank Fulvio Reggiori and Christian Ungermann for kindly providing the GNS1 plasmid. This work was supported by the Japan Society for the promotion of Science for J.Y.T., the Novartis Foundation (Japan), the Mitsubishi foundation, the Naito Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Futaba Electronics Memorial Foundation, the Astellas Foundation for Research on Metabolic Disorders, the Hamaguchi Foundation for the Advancement of Biochemistry, the Takeda Science Foundation and the Kurata Memorial Hitachi Science and Technology Foundation, to J.T.
Open access: yes (repository)