title: The scaffold protein EPG-7 links cargo-receptor complexes with the autophagic assembly machinery.
abstract: The mechanism by which protein aggregates are selectively degraded by autophagy is poorly understood. Previous studies show that a family of Atg8-interacting proteins function as receptors linking specific cargoes to the autophagic machinery. Here we demonstrate that during Caenorhabditis elegans embryogenesis, epg-7 functions as a scaffold protein mediating autophagic degradation of several protein aggregates, including aggregates of the p62 homologue SQST-1, but has little effect on other autophagy-regulated processes. EPG-7 self-oligomerizes and is degraded by autophagy independently of SQST-1. SQST-1 directly interacts with EPG-7 and colocalizes with EPG-7 aggregates in autophagy mutants. Mutations in epg-7 impair association of SQST-1 aggregates with LGG-1/Atg8 puncta. EPG-7 interacts with multiple ATG proteins and colocalizes with ATG-9 puncta in various autophagy mutants. Unlike core autophagy genes, epg-7 is dispensable for starvation-induced autophagic degradation of substrate aggregates. Our results indicate that under physiological conditions a scaffold protein endows cargo specificity and also elevates degradation efficiency by linking the cargo-receptor complex with the autophagic machinery.
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Long
authors.initials: L
authors.lastname: Lin
authors.forename: Peiguo
authors.initials: P
authors.lastname: Yang
authors.forename: Xinxin
authors.initials: X
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology*; D047108:Embryonic Development / Q000502:physiology*; D009154:Mutation; D055503:Protein Multimerization / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins