RRC ID 49523
Author Itoh T, Fujita N, Kanno E, Yamamoto A, Yoshimori T, Fukuda M.
Title Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation.
Journal Mol Biol Cell
Abstract Macroautophagy is a mechanism of degradation of cytoplasmic components in all eukaryotic cells. In macroautophagy, cytoplasmic components are wrapped by double-membrane structures called autophagosomes, whose formation involves unique membrane dynamics, i.e., de novo formation of a double-membrane sac called the isolation membrane and its elongation. However, the precise regulatory mechanism of isolation membrane formation and elongation remains unknown. In this study, we showed that Golgi-resident small GTPase Rab33B (and Rab33A) specifically interacts with Atg16L, an essential factor in isolation membrane formation, in a guanosine triphosphate-dependent manner. Expression of a GTPase-deficient mutant Rab33B (Rab33B-Q92L) induced the lipidation of LC3, which is an essential process in autophagosome formation, even under nutrient-rich conditions, and attenuated macroautophagy, as judged by the degradation of p62/sequestosome 1. In addition, overexpression of the Rab33B binding domain of Atg16L suppressed autophagosome formation. Our findings suggest that Rab33 modulates autophagosome formation through interaction with Atg16L.
Volume 19(7)
Pages 2916-25
Published 2008-7-1
DOI 10.1091/mbc.e07-12-1231
PII E07-12-1231
PMID 18448665
PMC PMC2441679
MeSH Animals Autophagy Autophagy-Related Proteins COS Cells Carrier Proteins / metabolism* Cell Membrane / metabolism Chlorocebus aethiops GTP Phosphohydrolases / metabolism* Gene Expression Regulation, Enzymologic* Golgi Apparatus / metabolism* HeLa Cells Humans Mice NIH 3T3 Cells Phagosomes / metabolism* rab GTP-Binding Proteins / metabolism*
IF 3.905
Times Cited 173
Resource
DNA material pEF-T7-mouse Atg5 (RDB15374) pEF-T7-mouse Atg12 (RDB15375) pEF-T7-mouse Atg16L1gamma (RDB15376) pEGFP-C1-mouse Rab33A (RDB15378) pEGFP-C1-mouse Rab33B (RDB15379) pEGFP-C1-mouse Rab33B-Q92L (RDB15380) pEGFP-C1-mouse Rab33B-T47N (RDB15381).