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 journalArticlepeer-review

21 Scopus citations

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 &αλπηα; 2 integrin to perinuclear multivesicular bodies, &αλπη α;2-MVBs. We show here that the internalized clustered &αλπηα;2 integrin remains in 〈2-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 &αλπ ηα;2 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 &αλπηα;2-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 (US)
Pages (from-to)448-463
Number of pages16
JournalMolecular Biology of the Cell
Volume23
Issue number3
DOIs
StatePublished - Feb 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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