title: A Vps21 endocytic module regulates autophagy.
abstract: In autophagy, the double-membrane autophagosome delivers cellular components for their degradation in the lysosome. The conserved Ypt/Rab GTPases regulate all cellular trafficking pathways, including autophagy. These GTPases function in modules that include guanine-nucleotide exchange factor (GEF) activators and downstream effectors. Rab7 and its yeast homologue, Ypt7, in the context of such a module, regulate the fusion of both late endosomes and autophagosomes with the lysosome. In yeast, the Rab5-related Vps21 is known for its role in early- to late-endosome transport. Here we show an additional role for Vps21 in autophagy. First, vps21∆ mutant cells are defective in selective and nonselective autophagy. Second, fluorescence and electron microscopy analyses show that vps21∆ mutant cells accumulate clusters of autophagosomal structures outside the vacuole. Third, cells with mutations in other members of the endocytic Vps21 module, including the GEF Vps9 and factors that function downstream of Vps21, Vac1, CORVET, Pep12, and Vps45, are also defective in autophagy and accumulate clusters of autophagosomes. Finally, Vps21 localizes to PAS. We propose that the endocytic Vps21 module also regulates autophagy. These findings support the idea that the two pathways leading to the lysosome--endocytosis and autophagy--converge through the Vps21 and Ypt7 GTPase modules.
authors.affiliation: College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Shenshen
authors.initials: S
authors.lastname: Zou
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Sidney
authors.initials: S
authors.lastname: Yu
authors.affiliation: Key Laboratory of Ecology and Environmental Science in Guangdong Higher Education, School of Life Science, South China Normal University, Guangzhou 510631, China.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Sciences and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Life Sciences and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Life Sciences and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Electron Microscope Demonstrating Co. Lab of Nanjing Agriculture University and Tianmei High-Tech Corporation, Nanjing 210095, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: He
authors.affiliation: Electron Microscope Demonstrating Co. Lab of Nanjing Agriculture University and Tianmei High-Tech Corporation, Nanjing 210095, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.affiliation: Key Laboratory of Ecology and Environmental Science in Guangdong Higher Education, School of Life Science, South China Normal University, Guangzhou 510631, China.
authors.forename: Lars Olof
authors.initials: LO
authors.lastname: Björn
authors.affiliation: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Lipatova
authors.affiliation: College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China liangyh@njau.edu.cn zxie@sjtu.edu.cn nava@uic.edu.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Life Sciences and Technology, Shanghai Jiao Tong University, Shanghai 200240, China liangyh@njau.edu.cn zxie@sjtu.edu.cn nava@uic.edu.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607 liangyh@njau.edu.cn zxie@sjtu.edu.cn nava@uic.edu.
authors.forename: Nava
authors.initials: N
authors.lastname: Segev
mesh_terms: D001343:Autophagy / Q000502:physiology*; D001692:Biological Transport; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D020691:rab GTP-Binding Proteins