Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway

Nina Rintanen, Mikko Karjalainen, Jonna Alanko, Lassi Paavolainen, Anita Mäki, Liisa Nissinen, Moona Lehkonen, Katri Kallio, R. Holland Cheng, Paula Upla, Johanna Ivaska, Varpu Marjomäki

Research output: Contribution to journalArticleScientificpeer-review

21 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)448-463
JournalMolecular Biology of the Cell
Volume23
Issue number3
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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    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, 23(3), 448-463. https://doi.org/10.1091/mbc.E11-06-0548