Calpains promote α2β1 integrin turnover in non-recycling integrin pathway.
Abstract
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.
Main Authors
Format
Articles
Research article
Published
2012
Series
Subjects
Publication in research information system
Publisher
American Society for Cell Biology
The permanent address of the publication
https://urn.fi/URN:NBN:fi:jyu-201811024614Use this for linking
Review status
Peer reviewed
ISSN
1059-1524
DOI
https://doi.org/10.1091/mbc.e11-06-0548
Language
English
Published in
Molecular Biology of the Cell
Citation
- 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 non-recycling integrin pathway.. Molecular Biology of the Cell, 23(3), 448-463. https://doi.org/10.1091/mbc.e11-06-0548
Copyright© 2012 Rintanen et al.