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PMID: 21220506 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.

The Journal of cell biology ·Vol. 192 ·No. 1 ·2011-01-10 ·Pages 17-27

Itakura E, Mizushima N

Abstract

Autophagy is an intracellular degradation process by which cytoplasmic contents are degraded in the lysosome. In addition to nonselective engulfment of cytoplasmic materials, the autophagosomal membrane can selectively recognize specific proteins and organelles. It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3. In this study, we analyzed loading of p62 and its related protein NBR1 and found that they localize to the endoplasmic reticulum (ER)-associated autophagosome formation site independently of LC3 localization to membranes. p62 colocalizes with upstream autophagy factors such as ULK1 and VMP1 even when autophagosome formation is blocked by wortmannin or FIP200 knockout. Self-oligomerization of p62 is essential for its localization to the autophagosome formation site. These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway.

MeSH Terms
Adaptor Proteins, Signal Transducing/chemistry,metabolism Animals Autophagy Endoplasmic Reticulum/metabolism Heat-Shock Proteins/chemistry,metabolism Humans Intracellular Signaling Peptides and Proteins Mice Microtubule-Associated Proteins/metabolism NIH 3T3 Cells Phagosomes/metabolism Phosphatidylethanolamines/metabolism Protein Binding Protein Structure, Quaternary Protein Structure, Tertiary Protein Transport Proteins/metabolism Sequestosome-1 Protein Structure-Activity Relationship
Chemicals
Adaptor Proteins, Signal Transducing Heat-Shock Proteins Intracellular Signaling Peptides and Proteins Map1lc3b protein, mouse Microtubule-Associated Proteins NBR1 protein, human Phosphatidylethanolamines Proteins Sequestosome-1 Protein Sqstm1 protein, mouse phosphatidylethanolamine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Itakura Eisuke
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Mizushima Noboru
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201009067
Published
2011-01-10
Pages
17-27
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC3019556
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.201009067 PMC Full Text View journal details
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