Back to Search
Start Over
Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway
- Source :
- Molecular Biology of the Cell, Molecular biology of the cell, vol 23, iss 3, Rintanen, N, Karjalainen, M, Alanko, J, Paavolainen, L, Mäki, A, Nissinen, L, Lehkonen, M, Kallio, K, Cheng, R H, Upla, P, Ivaska, J & Marjomäki, V 2012, ' Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway ', Molecular Biology of the Cell, vol. 23, no. 3, pp. 448-463 . https://doi.org/10.1091/mbc.E11-06-0548
- Publication Year :
- 2012
- Publisher :
- The American Society for Cell Biology, 2012.
-
Abstract
- A novel virus- and integrin clustering–specific pathway diverts integrin from its normal endo/exocytic traffic to a nonrecycling degradative endosomal route. Clustering of α2β1 integrin causes redistribution of the integrin to perinuclear endosomes, leading to enhanced integrin turnover promoted by calpains.<br />Collagen receptor integrins recycle between the plasma membrane and endosomes and facilitate formation and turnover of focal adhesions. In contrast, clustering of α2β1 integrin with antibodies or the human pathogen echovirus 1 (EV1) causes redistribution of α2 integrin to perinuclear multivesicular bodies, α2-MVBs. We show here that the internalized clustered α2 integrin remains in α2-MVBs and is not recycled back to the plasma membrane. Instead, receptor clustering and internalization lead to an accelerated down-regulation of α2β1 integrin compared to the slow turnover of unclustered α2 integrin. EV1 infection or integrin degradation is not associated with proteasomal or autophagosomal processes and shows no significant association with lysosomal pathway. In contrast, degradation is dependent on calpains, such that it is blocked by calpain inhibitors. We show that active calpain is present in α2-MVBs, internalized clustered α2β1 integrin coprecipitates with calpain-1, and calpain enzymes can degrade α2β1 integrin. In conclusion, we identified a novel virus- and clustering-specific pathway that diverts α2β1 integrin from its normal endo/exocytic traffic to a nonrecycling, calpain-dependent degradative endosomal route.
- Subjects :
- Endosome
Integrin
CD18
Medical and Health Sciences
CD49c
Cell Line
Collagen receptor
Focal adhesion
03 medical and health sciences
Cell Line, Tumor
Humans
Molecular Biology
030304 developmental biology
0303 health sciences
Focal Adhesions
Tumor
biology
Calpain
030302 biochemistry & molecular biology
Cell Membrane
Cell Biology
Articles
Biological Sciences
3. Good health
Cell biology
Enterovirus B, Human
Protein Transport
Integrin alpha M
Membrane Trafficking
biology.protein
Integrin, beta 6
Enterovirus B
Integrin alpha2beta1
Human
Developmental Biology
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19394586 and 10591524
- Volume :
- 23
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....eac14fbfb616914517938a7cf5da1210