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. There is a [Have you seen?][1] (February 2011) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.8
Significance: RNAs contain over 100 types of chemical modifications, and N6 -methyladenosine (m 6 A) is the most common internal modification in eukaryotic mRNA. m 6 A is involved in a variety of important biological processes, including sex determination in Drosophila , by modifying Sxl pre-mRNA and regulating its alternative splicing. m 6 A is installed by a large methyltransferase complex called the m 6 A “writer.” We have identified xio as a component of the Drosophila sex determination pathway based on its female-to-male transformation phenotypes. Xio interacts with other m 6 A writer subunits, and its loss of function shows typical phenotypes associated with other m 6 A factors, such as Sxl splicing misregulation, adult defects, and reduced m 6 A levels. Therefore, we conclude that Xio is a member of the m 6 A writer complex.
Autophagy and molecular chaperones both regulate protein homeostasis and maintain important physiological functions. Atg7 (autophagy-related gene 7) and Hsp27 (heat shock protein 27) are involved in the regulation of neurodegeneration and aging. However, the genetic connection between Atg7 and Hsp27 is not known.