Phosphorylation of Atg9 regulates movement to the phagophore assembly site and the rate of autophagosome formation.
Autophagy
; 12(4): 648-58, 2016.
Article
en En
| MEDLINE
| ID: mdl-27050455
ABSTRACT
Macroautophagy is primarily a degradative process that cells use to break down their own components to recycle macromolecules and provide energy under stress conditions, and defects in macroautophagy lead to a wide range of diseases. Atg9, conserved from yeast to mammals, is the only identified transmembrane protein in the yeast core macroautophagy machinery required for formation of the sequestering compartment termed the autophagosome. This protein undergoes dynamic movement between the phagophore assembly site (PAS), where the autophagosome precursor is nucleated, and peripheral sites that may provide donor membrane for expansion of the phagophore. Atg9 is a phosphoprotein that is regulated by the Atg1 kinase. We used stable isotope labeling by amino acids in cell culture (SILAC) to identify phosphorylation sites on this protein and identified an Atg1-independent phosphorylation site at serine 122. A nonphosphorylatable Atg9 mutant showed decreased autophagy activity, whereas the phosphomimetic mutant enhanced activity. Electron microscopy analysis suggests that the different levels of autophagy activity reflect differences in autophagosome formation, correlating with the delivery of Atg9 to the PAS. Finally, this phosphorylation regulates Atg9 interaction with Atg23 and Atg27.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
/
Autofagia
/
Proteínas de Saccharomyces cerevisiae
/
Autofagosomas
/
Proteínas Relacionadas con la Autofagia
/
Proteínas de la Membrana
Idioma:
En
Revista:
Autophagy
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos