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A Vps21 endocytic module regulates autophagy

Author:
  • Yong Chen
  • Fan Zhou
  • Shenshen Zhou
  • Sidney Yu
  • Shaoshan Li
  • Dan Li
  • Jingzhen Song
  • Hui Li
  • Zhiyi He
  • Bing Hu
  • Lars Olof Björn
  • Zhanna Lipotova
  • Yongheng Liang
  • Zhiping Xie
  • Nava Segev
Publishing year: 2014
Language: English
Pages: 3166-3177
Publication/Series: Molecular Biology of the Cell
Volume: 25
Issue: 20
Document type: Journal article
Publisher: American Society for Cell Biology

Abstract english

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, vps21Δ mutant cells are defective in selective and nonselective autophagy. Second, fluorescence and electron microscopy analyses show that vps21Δ 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.

Keywords

  • Biological Sciences

Other

Published
  • ISSN: 1939-4586
Lars Olof Björn
E-mail: lars_olof [dot] bjorn [at] biol [dot] lu [dot] se

Professor emeritus

Molecular Cell Biology

+46 46 222 72 53

B-A340

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