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Updated: Jan 22, 2026
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors
Terje Johansen1, Trond Lamark1
1Molecular Cancer Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
Abstract:
Selective 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- to 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. 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 selective autophagy receptor-coated cargo incorporating the latest findings is presented.
Insights
Selective autophagy uses cargo receptors to bind cargo and ATG8 proteins via LC3-interacting region (LIR) motifs. This review details LIR-ATG8 interactions and their role in autophagosome formation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Selective autophagy requires cargo receptors to target specific cargo for degradation.
- Cargo receptors link cargo to the autophagosome machinery via ATG8 family proteins.
- LC3-interacting region (LIR) motifs mediate interactions between cargo receptors and ATG8 proteins.
Purpose of the Study:
- To review the molecular mechanisms of LIR-ATG8 interactions in selective autophagy.
- To discuss the role of ATG8 proteins as membrane scaffolds.
- To present a model for phagophore recruitment and expansion in selective autophagy.
Main Methods:
- Literature review of selective autophagy research.
- Analysis of LIR-ATG8 interactions and specificity.
- Discussion of atypical and LIR-independent interactions.
Main Results:
- LIR motifs bind to the LIR docking site (LDS) on ATG8 proteins, mediating cargo recognition.
- Specificity in binding to GABARAP or LC3 subfamily proteins is achieved through distinct interactions.
- Soluble cargo receptors can recruit core autophagy components to facilitate autophagosome assembly.
Conclusions:
- LIR-ATG8 interactions are crucial for selective autophagy.
- ATG8 proteins act as key membrane scaffolds.
- A novel model integrating recent findings on phagophore recruitment and expansion is presented.
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