RRC ID 46471
著者 Wu F, Li Y, Wang F, Noda NN, Zhang H.
タイトル Differential function of the two Atg4 homologues in the aggrephagy pathway in Caenorhabditis elegans.
ジャーナル J Biol Chem
Abstract The presence of multiple homologues of the same yeast Atg protein endows an additional layer of complexity on the autophagy pathway in higher eukaryotes. The physiological function of the individual genes, however, remains largely unknown. Here we investigated the role of the two Caenorhabditis elegans homologues of the cysteine protease Atg4 in the pathway responsible for degradation of protein aggregates. Loss of atg-4.1 activity causes defective degradation of a variety of protein aggregates, whereas atg-4.2 mutants remove these substrates normally. LGG-1 precursors accumulate in atg-4.1 mutants, but not atg-4.2 mutants. LGG-1 puncta, formation of which depends on lipidation of LGG-1, are present in atg-4.1 and atg-4.2 single mutants, but are completely absent in atg-4.1; atg-4.2 double mutants. In vitro enzymatic analysis revealed that ATG-4.1 processes LGG-1 precursors about 100-fold more efficiently than ATG-4.2. Expression of a mutant form LGG-1, which mimics the processed precursor, rescues the defective autophagic degradation of protein aggregates in atg-4.1 mutants and, to a lesser extent, in atg-4.1; atg-4.2 double mutants. Our study reveals that ATG-4.1 and ATG-4.2 are functionally redundant yet display differential LGG-1 processing and deconjugating activity in the aggrephagy pathway in C. elegans.
巻・号 287(35)
ページ 29457-67
公開日 2012-8-24
DOI 10.1074/jbc.M112.365676
PII S0021-9258(20)63211-2
PMID 22767594
PMC PMC3436130
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / biosynthesis* Caenorhabditis elegans Proteins / genetics Cysteine Endopeptidases / biosynthesis* Cysteine Endopeptidases / genetics Gene Expression Regulation, Enzymologic / physiology* Mutation Proteolysis*
IF 4.238
引用数 28
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm3948