Document Detail


An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure.
MedLine Citation:
PMID:  18768752     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the process of autophagy, a ubiquitin-like molecule, LC3/Atg8, is conjugated to phosphatidylethanolamine (PE) and associates with forming autophagosomes. In mammalian cells, the existence of multiple Atg8 homologues (referred to as LC3 paralogues) has hampered genetic analysis of the lipidation of LC3 paralogues. Here, we show that overexpression of an inactive mutant of Atg4B, a protease that processes pro-LC3 paralogues, inhibits autophagic degradation and lipidation of LC3 paralogues. Inhibition was caused by sequestration of free LC3 paralogues in stable complexes with the Atg4B mutant. In mutant overexpressing cells, Atg5- and ULK1-positive intermediate autophagic structures accumulated. The length of these membrane structures was comparable to that in control cells; however, a significant number were not closed. These results show that the lipidation of LC3 paralogues is involved in the completion of autophagosome formation in mammalian cells. This study also provides a powerful tool for a wide variety of studies of autophagy in the future.
Authors:
Naonobu Fujita; Mitsuko Hayashi-Nishino; Hiromi Fukumoto; Hiroko Omori; Akitsugu Yamamoto; Takeshi Noda; Tamotsu Yoshimori
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-03
Journal Detail:
Title:  Molecular biology of the cell     Volume:  19     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-29     Completed Date:  2008-12-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4651-9     Citation Subset:  IM    
Affiliation:
Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy*
Catalysis
Cell Line
Cell Membrane / ultrastructure
Cysteine Endopeptidases / metabolism*
Green Fluorescent Proteins / metabolism
Humans
Lipid Metabolism*
Mice
Microtubule-Associated Proteins / metabolism*
Mutant Proteins / metabolism
Mutation / genetics*
Phagosomes / metabolism*,  ultrastructure
Phosphatidylethanolamines / metabolism
Recombinant Fusion Proteins / metabolism
Sequence Homology, Amino Acid*
Chemical
Reg. No./Substance:
0/Microtubule-Associated Proteins; 0/Mutant Proteins; 0/Phosphatidylethanolamines; 0/Recombinant Fusion Proteins; 0/light chain 3, human; 147336-22-9/Green Fluorescent Proteins; 39382-08-6/phosphatidylethanolamine; EC 3.4.22.-/Atg4bl protein, mouse; EC 3.4.22.-/Cysteine Endopeptidases
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