TAX1BP1 recruits ATG9 vesicles through SCAMP3 binding

Abstract

AbstractMacroautophagy is a cellular process that delivers cytoplasmic material to lysosomes for degradation via autophagosomes. It often involves the selective degradation of ubiquitinated proteins. During selective macroautophagy, five ubiquitin-binding adaptors, p62, NBR1, OPTN, NDP52, and TAX1BP1, form biomolecular condensates with ubiquitinated proteins and recruit ATG9 vesicles, which serve as the initial membrane source required for autophagosome formation. However, the molecular details underlying the cargo/adaptor-dependent recruitment of ATG9 vesicles remain unclear. Here, we show that ATG9 vesicles are recruited by three cargo adaptors: TAX1BP1, NBR1, and OPTN. We also find that ATG9A itself is not the determinant for recruitment by these cargo adaptors, and that TAX1BP1-dependent ATG9 vesicle recruitment is mediated by SCAMP3, a transmembrane protein on the ATG9 vesicles, through binding to the coiled-coil 1 domain of TAX1BP1. These findings provide mechanistic insights into the cargo/adaptor-dependent assembly of ATG9 vesicles in mammals.