title: Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation.
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.
authors.affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
authors.forename: Naonobu
authors.initials: N
authors.lastname: Fujita
authors.forename: Eiko
authors.initials: E
authors.lastname: Kanno
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010588:Phagosomes / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C518959:ATG16L1 protein, human; C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D020558:GTP Phosphohydrolases; C486397:RAB33B protein, human; C112838:Rab33B protein, mouse; D020691:rab GTP-Binding Proteins