Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
EMBO J. 2011 Feb 16;30(4):636-51. doi: 10.1038/emboj.2010.338. Epub 2010 Dec 17.
Autophagy is a membrane-mediated degradation process of macromolecule recycling. Although the formation of double-membrane degradation vesicles (autophagosomes) is known to have a central role in autophagy, the mechanism underlying this process remains elusive. The serine/threonine kinase Atg1 has a key role in the induction of autophagy. In this study, we show that overexpression of Drosophila Atg1 promotes the phosphorylation-dependent activation of the actin-associated motor protein myosin II. A novel myosin light chain kinase (MLCK)-like protein, Spaghetti-squash activator (Sqa), was identified as a link between Atg1 and actomyosin activation. Sqa interacts with Atg1 through its kinase domain and is a substrate of Atg1. Significantly, myosin II inhibition or depletion of Sqa compromised the formation of autophagosomes under starvation conditions. In mammalian cells, we found that the Sqa mammalian homologue zipper-interacting protein kinase (ZIPK) and myosin II had a critical role in the regulation of starvation-induced autophagy and mammalian Atg9 (mAtg9) trafficking when cells were deprived of nutrients. Our findings provide evidence of a link between Atg1 and the control of Atg9-mediated autophagosome formation through the myosin II motor protein.
自噬是一种大分子物质回收的膜介导降解过程。尽管双层膜降解囊泡（自噬体）的形成被认为在自噬中具有核心作用，但该过程的机制仍不清楚。丝氨酸/苏氨酸激酶 Atg1 在自噬的诱导中起着关键作用。在这项研究中，我们表明果蝇 Atg1 的过表达促进了肌球蛋白 II 相关的肌动蛋白依赖性马达蛋白的磷酸化激活。一种新的肌球蛋白轻链激酶（MLCK）样蛋白，Spaghetti-squash activator（Sqa），被鉴定为 Atg1 和肌动球蛋白激活之间的联系。Sqa 通过其激酶结构域与 Atg1 相互作用，并且是 Atg1 的底物。重要的是，在饥饿条件下，肌球蛋白 II 的抑制或 Sqa 的耗竭会损害自噬体的形成。在哺乳动物细胞中，我们发现 Sqa 的哺乳动物同源物拉链相互作用蛋白激酶（ZIPK）和肌球蛋白 II 在调节饥饿诱导的自噬和哺乳动物 Atg9（mAtg9）运输中起着关键作用，当细胞缺乏营养时。我们的研究结果提供了证据，表明 Atg1 与肌球蛋白 II 马达蛋白控制 Atg9 介导的自噬体形成之间存在联系。
