Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity.
Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity.
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DOI：
10.1091/mbc.e12-01-0010
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发表时间：
2012-08
影响因子：
3.3
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
作者：
Ishibashi K;Uemura T;Waguri S;Fukuda M
Atg16L1是自噬所必需的蛋白质，位于PC12细胞的致密核心囊泡上，Atg16L1的敲低抑制激素分泌，而不依赖于自噬。此外，Atg16L1与小的GTdR Rab33A相互作用，并且这种相互作用是Atg16L1的致密核心囊泡定位所必需的。自噬是所有真核细胞中存在的一种整体降解系统，调节着高等真核生物的多种生物学活动。最近，自噬参与分泌途径的调节也有报道，但将自噬与分泌途径联系起来的分子机制仍然很大程度上未知。在这里，我们表明，Atg16L1，典型的自噬的必需蛋白质，是本地化在神经内分泌PC12细胞中的含蛋白质的致密核心囊泡和Atg16L1的敲低导致激素分泌水平的显着降低独立的自噬活性。我们还发现，Atg16L1与小的GTdR Rab33A相互作用，这种相互作用是必需的致密核心囊泡定位的Atg16L1在PC12细胞。我们的研究结果表明，Atg16L1不仅调节所有细胞类型中的自噬，而且还调节致密核心囊泡的分泌，推测是通过充当Rab33A效应子，特别是细胞类型。
Atg16L1, a protein essential for autophagy, is localized on dense-core vesicles in PC12 cells, and knockdown of Atg16L1 inhibits hormone secretion independently of autophagy. In addition, Atg16L1 interacts with the small GTPase Rab33A, and this interaction is required for the dense-core vesicle localization of Atg16L1. Autophagy is a bulk degradation system in all eukaryotic cells and regulates a variety of biological activities in higher eukaryotes. Recently involvement of autophagy in the regulation of the secretory pathway has also been reported, but the molecular mechanism linking autophagy with the secretory pathway remains largely unknown. Here we show that Atg16L1, an essential protein for canonical autophagy, is localized on hormone-containing dense-core vesicles in neuroendocrine PC12 cells and that knockdown of Atg16L1 causes a dramatic reduction in the level of hormone secretion independently of autophagic activity. We also find that Atg16L1 interacts with the small GTPase Rab33A and that this interaction is required for the dense-core vesicle localization of Atg16L1 in PC12 cells. Our findings indicate that Atg16L1 regulates not only autophagy in all cell types, but also secretion from dense-core vesicles, presumably by acting as a Rab33A effector, in particular cell types.