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.
| Original language | English |
|---|---|
| Pages (from-to) | 2913-2932 |
| Number of pages | 20 |
| Journal | Cellular and Molecular Life Sciences |
| Volume | 66 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Sep 1 2009 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Cellular and Molecular Neuroscience
- Cell Biology
Cite this
A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions. / Hirota, Yuko; Tanaka, Yoshitaka.
In: Cellular and Molecular Life Sciences, Vol. 66, No. 17, 01.09.2009, p. 2913-2932.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A small GTPase, human Rab32, is required for the formation of autophagic vacuoles under basal conditions
AU - Hirota, Yuko
AU - Tanaka, Yoshitaka
PY - 2009/9/1
Y1 - 2009/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=68949214328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68949214328&partnerID=8YFLogxK
U2 - 10.1007/s00018-009-0080-9
DO - 10.1007/s00018-009-0080-9
M3 - Article
C2 - 19593531
AN - SCOPUS:68949214328
VL - 66
SP - 2913
EP - 2932
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 17
ER -