1. Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway
- Author
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Liisa Nissinen, R. Holland Cheng, Nina Rintanen, Lassi Paavolainen, Paula Upla, Johanna Ivaska, Anita Mäki, Mikko Karjalainen, Katri Kallio, Varpu Marjomäki, Moona Lehkonen, Jonna Alanko, and Parton, Robert G
- 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 - 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., 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.
- Published
- 2012