Direct link between Atg protein and small GTPase Rab: Atg16L functions as a potential Rab33 effector in mammals.
Atg16L is a factor that is essential for elongation of the isolation membrane (also called phagophore), a precursor of the autophagosome. Atg16L facilitates LC3/Atg8-conjugation to phosphatidylethanolamine by forming an oligomeric complex with Atg12-conjugated Atg5 and recruiting an LC3-Atg3 intermediate to elongating isolation membranes. Although Atg16L is responsible for the isolation membrane localization of the complex, the mechanism by which Atg16L is targeted to or recognizes isolation membranes remains largely unknown. We recently reported finding that Atg16L specifically and directly interacts with the Golgi-resident small GTPase Rab33B (and Rab33A) via the coiled-coil domain of Atg16L. Since expression of a GTPase-deficient mutant of Rab33B or the coiled-coil domain of Atg16L modulates macroautophagy (simply referred to as autophagy below), Atg16L (or the Atg12-5/16L complex) is likely to function as a specific effector molecule for Rab33 in autophagosome formation. Future study of the cross talk between Atg16L-mediated autophagosome formation and Rab33-mediated membrane trafficking should provide an important clue to unresolved issues in autophagosome formation, specifically, the membrane source of autophagosomes.
Fukuda
Mitsunori
M
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan. nori@mail.tains.tohoku.ac.jp
Itoh
Takashi
T
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010588:Phagosomes / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D020033:Protein Isoforms; D020691:rab GTP-Binding Proteins