Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy

EMBO J. 2011 Feb 16;30(4):636-51. doi: 10.1038/emboj.2010.338. Epub 2010 Dec 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Autophagy / genetics
  • Autophagy / physiology*
  • Autophagy-Related Protein-1 Homolog
  • Autophagy-Related Proteins
  • Cells, Cultured
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Gene Expression / physiology
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Myosin Type II / metabolism*
  • Myosin-Light-Chain Kinase / genetics
  • Myosin-Light-Chain Kinase / metabolism
  • Myosin-Light-Chain Kinase / physiology
  • Phagosomes / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Starvation / genetics
  • Starvation / metabolism*
  • Tissue Distribution

Substances

  • Atg9 protein, Drosophila
  • Autophagy-Related Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • Atg1 protein, Drosophila
  • Autophagy-Related Protein-1 Homolog
  • Protein-Serine-Threonine Kinases
  • Myosin-Light-Chain Kinase
  • Myosin Type II