生物
自噬体
细胞生物学
自噬
生物发生
液泡
PI3K/AKT/mTOR通路
磷脂酰肌醇
激酶
细胞质
信号转导
生物化学
基因
细胞凋亡
作者
Kanae Hitomi,Tetsuya Kotani,Nobuo N. Noda,Hirokazu Kimura,Hitoshi Nakatogawa
标识
DOI:10.1083/jcb.202210017
摘要
In macroautophagy, cellular components are sequestered within autophagosomes and transported to lysosomes/vacuoles for degradation. Although phosphatidylinositol 3-kinase complex I (PI3KCI) plays a pivotal role in the regulation of autophagosome biogenesis, little is known about how this complex localizes to the pre-autophagosomal structure (PAS). In Saccharomyces cerevisiae, PI3KCI is composed of PI3K Vps34 and conserved subunits Vps15, Vps30, Atg14, and Atg38. In this study, we discover that PI3KCI interacts with the vacuolar membrane anchor Vac8, the PAS scaffold Atg1 complex, and the pre-autophagosomal vesicle component Atg9 via the Atg14 C-terminal region, the Atg38 C-terminal region, and the Vps30 BARA domain, respectively. While the Atg14–Vac8 interaction is constitutive, the Atg38–Atg1 complex interaction and the Vps30–Atg9 interaction are enhanced upon macroautophagy induction depending on Atg1 kinase activity. These interactions cooperate to target PI3KCI to the PAS. These findings provide a molecular basis for PAS targeting of PI3KCI during autophagosome biogenesis.
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