title: Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy.
abstract: 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.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Tang
authors.forename: Yu-Bao
authors.initials: YB
authors.lastname: Wang
authors.forename: Shiu-Lan
authors.initials: SL
authors.lastname: Wang
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Wu
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lin
authors.forename: Guang-Chao
authors.initials: GC
authors.lastname: Chen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D002478:Cells, Cultured; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D024462:Myosin Type II / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013217:Starvation / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C557894:Atg9 protein, Drosophila; D000071183:Autophagy-Related Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; C518074:Atg1 protein, Drosophila; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; D009219:Myosin-Light-Chain Kinase; D024462:Myosin Type II