RRC ID |
72408
|
著者 |
Itakura E, Mizushima N.
|
タイトル |
p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.
|
ジャーナル |
J Cell Biol
|
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.
|
巻・号 |
192(1)
|
ページ |
17-27
|
公開日 |
2011-1-10
|
DOI |
10.1083/jcb.201009067
|
PII |
jcb.201009067
|
PMID |
21220506
|
PMC |
PMC3019556
|
MeSH |
Adaptor Proteins, Signal Transducing / chemistry*
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Autophagy*
Endoplasmic Reticulum / metabolism
Heat-Shock Proteins / chemistry*
Heat-Shock Proteins / 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
|
IF |
8.811
|
リソース情報 |
遺伝子材料 |
pMXs-puro-GFP-p62 (RDB19628)
pMXs-IP-GFP-NBR1 (RDB19629)
pMXs-puro-GFP-p62 K7A, D69A (RDB19794)
pMXs-puro-GFP-p62 D337, 338, 339A (RDB19796)
pMXs-puro GFP-p62 dC (RDB19801) |