Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation

Suzuki Sho W.; Yamamoto Hayashi; Oikawa YuKondo-Kakuta ChikaKimura YayoiHirano HisashiOhsumi Yoshinori

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Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation

机译：Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation

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摘要

During autophagosome formation, autophagosome-related (Atg) proteins are recruited hierarchically to organize the preautophagosomal structure (PAS). Atg13, which plays a central role in the initial step of PAS formation, consists of two structural regions, the N-terminal HORMA (from Hop1, Rev7, and Mad2) domain and the C-terminal disordered region. The C-terminal disordered region of Atg13, which contains the binding sites for Atg1 and Atg17, is essential for the initiation step in which the Atg1 complex is formed to serve as a scaffold for the PAS. The N-terminal HORMA domain of Atg13 is also essential for autophagy, but its molecular function has not been established. In this study, we searched for interaction partners of the Atg13 HORMA domain and found that it binds Atg9, a multispanning membrane protein that exists on specific cytoplasmic vesicles (Atg9 vesicles). After the Atg1 complex is formed, Atg9 vesicles are recruited to the PAS and become part of the autophagosomal membrane. HORMA domain mutants, which are unable to interact with Atg9, impaired the PAS localization of Atg9 vesicles and exhibited severe defects in starvation-induced autophagy. Thus, Atg9 vesicles are recruited to the PAS via the interaction with the Atg13 HORMA domain. Based on these findings, we propose that the two distinct regions of Atg13 play crucial roles in distinct steps of autophagosome formation: In the first step, Atg13 forms a scaffold for the PAS via its C-terminal disordered region, and subsequently it recruits Atg9 vesicles via its N-terminal HORMA domain.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第11期|3350-3355|共6页
作者
Suzuki Sho W.; Yamamoto Hayashi; Oikawa YuKondo-Kakuta ChikaKimura YayoiHirano HisashiOhsumi Yoshinori;
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作者单位

Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Frontier Res Ctr, Yokohama, Kanagawa 2268501, Japan;

Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 2360004, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
autophagy; Atg13; Atg9; HORMA domain;

Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation

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