ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIβ
D Judith, HBJ Jefferies, S Boeing, D Frith… - Journal of Cell …, 2019 - rupress.org
Journal of Cell Biology, 2019•rupress.org
ATG9A is a multispanning membrane protein essential for autophagy. Normally resident in
Golgi membranes and endosomes, during amino acid starvation, ATG9A traffics to sites of
autophagosome formation. ATG9A is not incorporated into autophagosomes but is proposed
to supply so-far-unidentified proteins and lipids to the autophagosome. To address this
function of ATG9A, a quantitative analysis of ATG9A-positive compartments immunoisolated
from amino acid–starved cells was performed. These ATG9A vesicles are depleted of Golgi …
Golgi membranes and endosomes, during amino acid starvation, ATG9A traffics to sites of
autophagosome formation. ATG9A is not incorporated into autophagosomes but is proposed
to supply so-far-unidentified proteins and lipids to the autophagosome. To address this
function of ATG9A, a quantitative analysis of ATG9A-positive compartments immunoisolated
from amino acid–starved cells was performed. These ATG9A vesicles are depleted of Golgi …
ATG9A is a multispanning membrane protein essential for autophagy. Normally resident in Golgi membranes and endosomes, during amino acid starvation, ATG9A traffics to sites of autophagosome formation. ATG9A is not incorporated into autophagosomes but is proposed to supply so-far-unidentified proteins and lipids to the autophagosome. To address this function of ATG9A, a quantitative analysis of ATG9A-positive compartments immunoisolated from amino acid–starved cells was performed. These ATG9A vesicles are depleted of Golgi proteins and enriched in BAR-domain containing proteins, Arfaptins, and phosphoinositide-metabolizing enzymes. Arfaptin2 regulates the starvation-dependent distribution of ATG9A vesicles, and these ATG9A vesicles deliver the PI4-kinase, PI4KIIIβ, to the autophagosome initiation site. PI4KIIIβ interacts with ATG9A and ATG13 to control PI4P production at the initiation membrane site and the autophagic response. PI4KIIIβ and PI4P likely function by recruiting the ULK1/2 initiation kinase complex subunit ATG13 to nascent autophagosomes.
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