Atg23 and Atg27 act at the early stages of Atg9 trafficking in S. cerevisiae.
Atg9 is a conserved multipass transmembrane protein with an essential role in autophagy. In Saccharomyces cerevisiae, it travels through the secretory pathway to a unique compartment, the Atg9 peripheral structures. These structures are then targeted to the phagophore assembly site (PAS), where they are proposed to help deliver membrane to the forming autophagosome. We used 'in vivo reconstitution' of this process in a multiple-knockout strain to define four proteins, Atg11, Atg19, Atg23 and Atg27, as the core minimal machinery necessary and sufficient for the trafficking of Atg9 to the PAS. Atg23 and Atg27 function in the formation of the Atg9 peripheral structures. Overexpression of Atg9 can bypass the need for Atg23, suggesting that the amount of Atg9 in each peripheral structure is a critical factor in their targeting to the PAS. In contrast, overexpression of Atg23 or Atg27 interferes with Atg9 trafficking, suggesting that these proteins must be present in the appropriate stoichiometry in order to function properly. These data allow us to resolve existing controversies regarding the role of Atg23 and Atg27, and propose a model that ties together previous observations regarding the role of Atg9 in autophagosome formation.
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA; Current address: Department of Chemistry, Eastern Michigan University, Ypsilanti, MI, USA.
Steven K
SK
Backues
Daniel P
DP
Orban
Amélie
A
Bernard
Kushal
K
Singh
Yang
Y
Cao
Daniel J
DJ
Klionsky
D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
C434480:ATG19 protein, S cerevisiae; C519194:ATG27 protein, S cerevisiae; C434065:ATG9 protein, S cerevisiae; C502923:Atg11 protein, S cerevisiae; C480170:Atg23 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins
Cvt pathway; Golgi; autophagy; clustering; phagophore assembly site; sorting; trafficking