Updated in 7/4/2016 5:46:19 PM      Viewed: 211 times      (Journal Article)
Molecular biology of the cell 19 (7): 2916-25 (2008)

Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation.

Takashi Itoh , Naonobu Fujita , Eiko Kanno , Akitsugu Yamamoto , Tamotsu Yoshimori , Mitsunori Fukuda
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.
DOI: 10.1091/mbc.E07-12-1231      ISSN: 1059-1524