Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation
Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation
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DOI：
10.1091/mbc.e07-12-1231
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发表时间：
2008-07-01
影响因子：
3.3
通讯作者：
Fukuda, Mitsunori
中科院分区：
文献类型：
--
作者：
Itoh, Takashi;Fujita, Naonobu;Fukuda, Mitsunori
大自噬是真核细胞中细胞质成分降解的一种机制。在宏自噬中，细胞质成分被称为自噬体的双膜结构包裹，其形成涉及独特的膜动力学，即，从头形成一个双膜囊称为隔离膜和它的延长。然而，隔离膜形成和延伸的精确调节机制仍然未知。在这项研究中，我们发现，高尔基体居民的小GTdR Rab 33 B（和Rab 33 A）特异性相互作用与Atg 16 L，隔离膜形成的一个重要因素，在一个鸟苷三磷酸依赖的方式。GTP酶缺陷型突变体Rab 33 B（Rab 33 B-Q92 L）的表达诱导了LC 3的脂化，这是自噬体形成的一个重要过程，即使在营养丰富的条件下，也会减弱巨自噬，这是通过p62/螯合体1的降解来判断的。此外，Atg 16 L的Rab 33 B结合结构域的过表达抑制自噬体的形成。我们的研究结果表明Rab 33通过与Atg 16 L相互作用来调节自噬体的形成。
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.