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Vol. 19, Issue 7, 2916-2925, July 2008

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

Takashi Itoh^*, Naonobu Fujita, Eiko Kanno^*, Akitsugu Yamamoto, Tamotsu Yoshimori, and Mitsunori Fukuda^*

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

Submitted December 11, 2007; Revised March 28, 2008; Accepted April 18, 2008
Monitoring Editor: Akihiko Nakano

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.

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

Abbreviations used: GFP, green fluorescent protein; GST, glutathione transferase; HRP, horseradish peroxidase; PE, phosphatidylethanolamine; SQSTM1, sequestosome 1; Ubl, ubiquitin-like protein.