CALCOCO2/NDP52 initiates selective autophagy through recruitment of ULK and TBK1 kinase complexes

Abstract

The selective macroautophagy of prospective cargo necessitates activity of the autophagy machinery at cargo-determined locations. Whether phagophore membranes are recruited to, or are generated de novo at, the cargo is unknown. In our recent study we show that damaged Salmonella-containing vacuoles, marked by LGALS8/galectin-8, engage the cargo receptor CALCOCO2/NDP52 to recruit the autophagy-initiating ULK and TBK1 complexes and cause the formation of WIPI2-positive phagophore membranes. CALCOCO2 functions in the induction of autophagy by forming a trimer with RB1CC1/FIP200 and TBKBP1/SINTBAD-AZI2/NAP1, components of the ULK and TBK1 kinase complexes, respectively. Such recruitment of the upstream autophagy machinery to prospective cargo reveals how in complex eukaryotes detection of cargo-associated 'eat me' signals, induction of autophagy, and juxtaposition of cargo and phagophores are integrated.

Keywords: Autophagy; FIP200; NDP52; Salmonella; TBK1; ULK1; cargo receptor; eat-me signal; galectin-8.

Figure 1.

CALCOCO2/NDP52 orchestrates xenophagy by (1) detecting the ‘eat-me’ ligand LGALS8/galectin-8 on damaged SCVs, (2) initiating phagophore membrane formation by recruiting the ULK and TBK1 kinase complexes and (3) tethering damaged SCVs to the phagophore via LC3C.