Phosphatidylinositol 3-kinase and COPII generate LC3 lipidation vesicles from the ER-Golgi intermediate compartment.
Phosphatidylinositol 3-kinase and COPII generate LC3 lipidation vesicles from the ER-Golgi intermediate compartment.
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DOI：
10.7554/elife.04135
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发表时间：
2014-11-28
期刊：
影响因子：
7.7
通讯作者：
Schekman R
中科院分区：
文献类型：
--
作者：
Ge L;Zhang M;Schekman R
自噬体的形成需要来自细胞器的显著膜输入。然而，没有直接的证据已经发展到链接自噬因子和动员膜产生的吞噬细胞。先前，我们建立了无细胞LC 3脂化反应以鉴定ER-高尔基中间室（ERGIC）作为LC 3脂化的膜源，LC 3脂化是自噬体生物发生的关键步骤（Ge et al.，eLife 2013; 2：e00947）。我们现在报告，饥饿激活的自噬磷脂酰肌醇-3激酶（PI 3 K）诱导产生的小泡活性LC 3脂化。亚细胞分级分离研究确定ERGIC作为供体膜的小脂质活性囊泡的产生。依赖于活性PI 3 K，COPII蛋白被募集到饥饿细胞中的ERGIC膜。我们的结论是，饥饿激活自噬PI 3 K，这反过来又诱导COPII的招聘ERGIC芽LC 3脂质活性囊泡作为一个潜在的膜源的自噬体。DOI：http://dx.doi.org/10.7554/eLife.04135.001网站
Formation of the autophagosome requires significant membrane input from cellular organelles. However, no direct evidence has been developed to link autophagic factors and the mobilization of membranes to generate the phagophore. Previously, we established a cell-free LC3 lipidation reaction to identify the ER-Golgi intermediate compartment (ERGIC) as a membrane source for LC3 lipidation, a key step of autophagosome biogenesis (Ge et al., eLife 2013; 2:e00947). We now report that starvation activation of autophagic phosphotidylinositol-3 kinase (PI3K) induces the generation of small vesicles active in LC3 lipidation. Subcellular fractionation studies identified the ERGIC as the donor membrane in the generation of small lipidation-active vesicles. COPII proteins are recruited to the ERGIC membrane in starved cells, dependent on active PI3K. We conclude that starvation activates the autophagic PI3K, which in turn induces the recruitment of COPII to the ERGIC to bud LC3 lipidation-active vesicles as one potential membrane source of the autophagosome. DOI: http://dx.doi.org/10.7554/eLife.04135.001