Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors

Publication date: Available online 13 July 2019Source: Journal of Molecular BiologyAuthor(s): Terje Johansen, Trond LamarkAbstractSelective autophagy relies on soluble or membrane-bound cargo receptors that recognize cargo and bring about autophagosome formation at the cargo. The cargo-bound receptors interact with lipidated ATG8 family proteins anchored in the membrane at the concave side of the forming autophagosome. The interaction is mediated by 15-20 amino acid long sequence motifs called LC3-interacting region (LIR) motifs that bind to the LIR docking site (LDS) of ATG8 proteins. In this review we focus on LIR-ATG8 interactions and the soluble mammalian selective autophagy receptors (SARs). We discuss the roles of ATG8 family proteins as membrane scaffolds in autophagy and the LIR-LDS interaction and how specificity for binding to GABARAP or LC3 subfamily proteins is achieved. We also discuss atypical LIR-LDS interactions and a novel LIR-independent interaction. Recently, it has become clear that several of the soluble cargo receptors are able to recruit components of the core autophagy apparatus to aid in assembling autophagosome formation at the site of cargo sequestration. A model on phagophore recruitment and expansion on a SAR-coated cargo incorporating the latest findings is presented.Graphical abstract

Source: Journal of Molecular Biology - July 15, 2019 Category: Molecular Biology Source Type: research