Receptor proteins in selective autophagy

Abstract

Autophagy has long been thought to be an essential but unselective bulk degradation pathway. However, increasing evidence suggests selective autophagosomal turnover of a broad range of substrates. Bifunctional autophagy receptors play a key role in selective autophagy by tethering cargo to the site of autophagosomal engulfment. While the identity of molecular components involved in selective autophagy has been revealed at least to some extent, we are only beginning to understand how selectivity is achieved in this process. Here, we summarize the mechanistic and structural basis of receptor-mediated selective autophagy.

Figure 1

(a) Overview of selective autophagy. Boxes indicate localization of ATG8 and autophagy receptor proteins. (b) Scheme of autophagy receptor function. (c) Different cargo-binding concepts of autophagy receptors. (d) Domain architecture of the known characterized autophagy receptors.

Figure 2

(a) ATG8 conjugation cascade. (b) Structures of MAP1LC3B/p62-LIR (upper left; pdb code: 2K6Q) and GABARAPL1/NBR1-LIR (upper right; pdb code: 2ZJD) complexes. LIR binding sites of MAP1LC3B (lower left) and GABARAPL1 (lower right). (c) Sequence alignments of functional LIR motifs in autophagy receptors.