Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation.
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.
Itoh
Takashi
T
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
Fujita
Naonobu
N
Kanno
Eiko
E
Yamamoto
Akitsugu
A
Yoshimori
Tamotsu
T
Fukuda
Mitsunori
M
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*
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