A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions |
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Authors: | Yuko Hirota Yoshitaka Tanaka |
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Institution: | (1) Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan |
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Abstract: | Here we show that a small GTPase, Rab32, is a novel protein required for the formation of autophagic vacuoles. We found that
the wild-type or GTP-bound form of human Rab32 expressed in HeLa and COS cells is predominantly localized to the endoplasmic
reticulum (ER), and overexpression induces the formation of autophagic vacuoles containing an autophagosome marker protein
LC3, the ER-resident protein calnexin and endosomal/lysosomal membrane protein LAMP-2, even under nutrient-rich conditions.
The recruitment of Rab32 to the ER membrane was necessary for autophagic vacuole formation, suggesting involvement of the
ER as a source of autophagosome membranes. In contrast, the expression of the inactive form of, or siRNA-specific for, Rab32
caused the formation of p62/SQSTM1 and ubiquitinated protein-accumulating aggresome-like structures and significantly prevented
constitutive autophagy. We postulate that Rab32 facilitates the formation of autophagic vacuoles whose membranes are derived
from the ER and regulates the clearance of aggregated proteins by autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Rab32 Autophagy Aggresome p62/SQSTM1 LC3 |
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