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MBC in Press, published online ahead of print April 30, 2008
Mol. Biol. Cell 10.1091/mbc.E07-12-1231

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Submitted on December 11, 2007
Revised on March 28, 2008
Accepted on April 18, 2008

Golgi-resident Small GTPase Rab33B Interacts with Atg16L and Modulates Autophagosome Formation

Takashi Itoh,* Naonobu Fujita,{dagger} Eiko Kanno,* Akitsugu Yamamoto,{ddagger} Tamotsu Yoshimori,{dagger} and Mitsunori Fukuda*

*Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan; {dagger}Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; {ddagger}Department of Cell Biology, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan

Monitoring Editor: Akihiko Nakano

Macroautophagy is a mechanism of degradation of cytoplasmic components in all eukaryotic cells. In the process of 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 GTP-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/SQSTM1 (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.


Address correspondence to: Mitsunori Fukuda (nori{at}mail.tains.tohoku.ac.jp)







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