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

18 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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Calpain
Integrins
Cluster Analysis
Echovirus Infections
Cell Membrane
Collagen Receptors
Multivesicular Bodies
Human Enterovirus B
Focal Adhesions
Endosomes
Down-Regulation
Viruses

Cite this

Rintanen, N., Karjalainen, M., Alanko, J., Paavolainen, L., Mäki, A., Nissinen, L., ... 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
Rintanen, Nina ; Karjalainen, Mikko ; Alanko, Jonna ; Paavolainen, Lassi ; Mäki, Anita ; Nissinen, Liisa ; Lehkonen, Moona ; Kallio, Katri ; Cheng, R. Holland ; Upla, Paula ; Ivaska, Johanna ; Marjomäki, Varpu. / Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway. In: Molecular Biology of the Cell. 2012 ; Vol. 23, No. 3. pp. 448-463.
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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.",
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Rintanen, N, Karjalainen, M, Alanko, J, Paavolainen, L, Mäki, A, Nissinen, L, Lehkonen, M, Kallio, K, Cheng, RH, 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

Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway. / Rintanen, Nina; Karjalainen, Mikko; Alanko, Jonna; Paavolainen, Lassi; Mäki, Anita; Nissinen, Liisa; Lehkonen, Moona; Kallio, Katri; Cheng, R. Holland; Upla, Paula; Ivaska, Johanna; Marjomäki, Varpu.

In: Molecular Biology of the Cell, Vol. 23, No. 3, 2012, p. 448-463.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway

AU - Rintanen, Nina

AU - Karjalainen, Mikko

AU - Alanko, Jonna

AU - Paavolainen, Lassi

AU - Mäki, Anita

AU - Nissinen, Liisa

AU - Lehkonen, Moona

AU - Kallio, Katri

AU - Cheng, R. Holland

AU - Upla, Paula

AU - Ivaska, Johanna

AU - Marjomäki, Varpu

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1091/mbc.E11-06-0548

DO - 10.1091/mbc.E11-06-0548

M3 - Article

VL - 23

SP - 448

EP - 463

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 3

ER -

Rintanen N, Karjalainen M, Alanko J, Paavolainen L, Mäki A, Nissinen L et al. Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway. Molecular Biology of the Cell. 2012;23(3):448-463. https://doi.org/10.1091/mbc.E11-06-0548