Early Steps in Autophagy Depend on Direct Phosphorylation of Atg9 by the Atg1 Kinase
| Autor: | Daniel Papinski, Martina Schuschnig, Wolfgang Reiter, Larissa Wilhelm, Christopher A. Barnes, Alessio Maiolica, Isabella Hansmann, Thaddaeus Pfaffenwimmer, Monika Kijanska, Ingrid Stoffel, Sung Sik Lee, Andrea Brezovich, Jane Hua Lou, Benjamin E. Turk, Ruedi Aebersold, Gustav Ammerer, Matthias Peter, Claudine Kraft |
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| Rok vydání: | 2014 |
| Předmět: |
0106 biological sciences
Saccharomyces cerevisiae Proteins Molecular Sequence Data Autophagy-Related Proteins Saccharomyces cerevisiae Aminopeptidases 01 natural sciences Mass Spectrometry Article 03 medical and health sciences Phagosomes Consensus Sequence Autophagy Amino Acid Sequence Phosphorylation Molecular Biology 030304 developmental biology 0303 health sciences Binding Sites Arabidopsis Proteins Membrane Proteins Intracellular Membranes Cell Biology 3. Good health Erratum Protein Kinases 010606 plant biology & botany |
| Zdroj: | Molecular Cell Molecular Cell, 53 (3) Molecular cell Europe PubMed Central |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2013.12.011 |
| Popis: | Summary Bulk degradation of cytoplasmic material is mediated by a highly conserved intracellular trafficking pathway termed autophagy. This pathway is characterized by the formation of double-membrane vesicles termed autophagosomes engulfing the substrate and transporting it to the vacuole/lysosome for breakdown and recycling. The Atg1/ULK1 kinase is essential for this process; however, little is known about its targets and the means by which it controls autophagy. Here we have screened for Atg1 kinase substrates using consensus peptide arrays and identified three components of the autophagy machinery. The multimembrane-spanning protein Atg9 is a direct target of this kinase essential for autophagy. Phosphorylated Atg9 is then required for the efficient recruitment of Atg8 and Atg18 to the site of autophagosome formation and subsequent expansion of the isolation membrane, a prerequisite for a functioning autophagy pathway. These findings show that the Atg1 kinase acts early in autophagy by regulating the outgrowth of autophagosomal membranes. Graphical Abstract Highlights • The Atg1 kinase phosphorylation consensus was identified on peptide arrays • Atg9 is a direct target of the Atg1/ULK1 kinase in vitro and in vivo • Atg9 phosphorylation recruits Atg18 and Atg8 to the PAS • Atg9 phosphorylation is required for isolation membrane expansion/autophagy function Autophagy function is pivotal to cell health. Papinski et al. identify the phosphorylation consensus of the central kinase in this pathway, Atg1. The autophagy-related protein Atg9 is a direct target of Atg1. Atg9 phosphorylation by Atg1 is required for autophagosome formation. This finding sheds light on how Atg1 controls autophagy. |
| Databáze: | OpenAIRE |
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