Autophagy-related protein 9A

Definition:

Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion. Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome. Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion. Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1. In addition to autophagy, also plays a role in necrotic cell death (By similarity).

References:

[1]. Kristiane Søreng, et al. SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting Dynamin-2. EMBO Rep. 2018 Apr;19(4):e44837. [Content Brief]

[2]. Carlos M Guardia, et al. Structure of Human ATG9A, the Only Transmembrane Protein of the Core Autophagy Machinery. Cell Rep. 2020 Jun 30;31(13):107837. [Content Brief]

[3]. Shintaro Maeda, et al. Structure, lipid scrambling activity and role in autophagosome formation of ATG9A. Nat Struct Mol Biol. 2020 Dec;27(12):1194-1201. [Content Brief]

[4]. Andrew R J Young, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006 Sep 15;119(Pt 18):3888-900. [Content Brief]

[5]. Eleftherios Karanasios, et al. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles. Nat Commun. 2016 Aug 11;7:12420. [Content Brief]

[6]. Anthony Ravussin, et al. The phosphatidylinositol 3-phosphate-binding protein SNX4 controls ATG9A recycling and autophagy. J Cell Sci. 2021 Feb 10;134(3):jcs250670. [Content Brief]

[7]. Delphine Judith, et al. ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIβ. J Cell Biol. 2019 May 6;218(5):1634-1652. [Content Brief]

[8]. A Orsi, et al. Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell. 2012 May;23(10):1860-73. [Content Brief]

[9]. Zuriñe Antón, et al. A heterodimeric SNX4--SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly. J Cell Sci. 2020 Jul 15;133(14):jcs246306. [Content Brief]

[10]. Alireza Ghanbarpour, et al. A model for a partnership of lipid transfer proteins and scramblases in membrane expansion and organelle biogenesis. Proc Natl Acad Sci U S A. 2021 Apr 20;118(16):e2101562118. [Content Brief]

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