Abstract
Calpains form a family of Ca2+-dependent cysteine proteases involved in diverse cellular processes. However, the specific functions of each calpain isoform remain unknown. Recent reports have shown that calpain 2 (Capn2) is essential for cell viability. We have recently shown that Capn2 is a nuclear protease associated with chromosomes during mitosis in mammalian embryonic cells. We now report that Capn2 depletion impairs mitosis and induces apoptosis in murine cells. Low Capn2 levels induce chromosome alignment defects, the loss of histone H3 threonine 3 phosphorylation at centromeres, and premature sister chromatid separation. Thus, Capn2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Choi YH, Lee SJ, Nguyen P, Jang JS, Lee J, Wu ML, Takano E, Maki M, Henkart PA, Trepel JB (1997) Regulation of cyclin D1 by calpain protease. J Biol Chem 272:28479–28484
Dai J, Sultan S, Taylor SS, Higgins JM (2005) The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev 19:472–488
Dai J, Sullivan BA, Higgins JM (2006) Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Dev Cell 11:741–750
Dutt P, Croall DE, Arthur JS, Veyra TD, Williams K, Elce JS, Greer PA (2006) m-Calpain is required for preimplantation embryonic development in mice. BMC Dev Biol 6:3
Eot-Houllier G, Fulcrand G, Watanabe Y, Magnaghi-Jaulin L, Jaulin C (2008) Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister chromatid cohesion. Genes Dev 22:2639–2644
Goll DE, Thompson VF, Li H, Wei W, Cong J (2003) The calpain system. Physiol Rev 83:731–801
Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Mehes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N (2004) Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 36:1159–1161
Hata S, Sorimachi H, Nakagawa K, Maeda T, Abe K, Suzuki K (2001) Domain II of m-calpain is a Ca(2+)-dependent cysteine protease. FEBS Lett 501:111–114
Honda S, Marumoto T, Hirota T, Nitta M, Arima Y, Ogawa M, Saya H (2004) Activation of m-calpain is required for chromosome alignment on the metaphase plate during mitosis. J Biol Chem 279:10615–10623
Janossy J, Ubezio P, Apati A, Magocsi M, Tompa P, Friedrich P (2004) Calpain as a multi-site regulator of cell cycle. Biochem Pharmacol 67:1513–1521
Kubbutat MH, Vousden KH (1997) Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability. Mol Cell Biol 17:460–468
Lane RD, Allan DM, Mellgren RL (1992) A comparison of the intracellular distribution of mu-calpain, m-calpain, and calpastatin in proliferating human A431 cells. Exp Cell Res 203:5–16
Magnaghi-Jaulin L, Eot-Houllier G, Fulcrand G, Jaulin C (2007) Histone deacetylase inhibitors induce premature sister chromatid separation and override the mitotic spindle assembly checkpoint. Cancer Res 67:6360–6367
McGuinness BE, Hirota T, Kudo NR, Peters JM, Nasmyth K (2005) Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells. PLoS Biol 3:e86
Mellgren RL, Song K, Mericle MT (1993) m-Calpain requires DNA for activity on nuclear proteins at low calcium concentrations. J Biol Chem 268:653–657
Michel LS, Liberal V, Chatterjee A, Kirchwegger R, Pasche B, Gerald W, Dobles M, Sorger PK, Murty VV, Benezra R (2001) MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409:355–359
O’Connell BC, Harper JW (2007) Ubiquitin proteasome system (UPS): what can chromatin do for you? Curr Opin Cell Biol 19:206–214
Patel YM, Lane MD (2000) Mitotic clonal expansion during preadipocyte differentiation: calpain-mediated turnover of p27. J Biol Chem 275:17653–17660
Raynaud F, Carnac G, Marcilhac A, Benyamin Y (2004) m-Calpain implication in cell cycle during muscle precursor cell activation. Exp Cell Res 298:48–57
Raynaud F, Marcilhac A, Chebli K, Benyamin Y, Rossel M (2008) Calpain 2 expression pattern and sub-cellular localization during mouse embryogenesis. Int J Dev Biol 52:383–388
Rios-Doria J, Kuefer R, Ethier SP, Day ML (2004) Cleavage of beta-catenin by calpain in prostate and mammary tumor cells. Cancer Res 64:7237–7240
Schollmeyer JE (1988) Calpain II involvement in mitosis. Science 240:911–913
Shiba E, Kim S, Fujitani M, Kambayashi JI, Kawamura I, Tsujimoto S, Shimomura K, Tanji Y, Taguchi T, Kimoto Y, Izukura M, Takai SI (1996) Possible involvement of calpain in the growth of estrogen receptor positive breast cancer cells. Anticancer Res 16:773–777
Sonoda E, Matsusaka T, Morrison C, Vagnarelli P, Hoshi O, Ushiki T, Nojima K, Fukagawa T, Waizenegger IC, Peters JM, Earnshaw WC, Takeda S (2001) Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev Cell 1:759–770
Watanabe Y (2005) Shugoshin: guardian spirit at the centromere. Curr Opin Cell Biol 17:590–595
Xu Y, Mellgren RL (2002) Calpain inhibition decreases the growth rate of mammalian cell colonies. J Biol Chem 277:21474–21479
Yaffe D, Saxel O (1977) Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature 270:725–727
Zyss D, Montcourrier P, Vidal B, Anguille C, Merezegue F, Sahuquet A, Mangeat PH, Coopman PJ (2005) The Syk tyrosine kinase localizes to the centrosomes and negatively affects mitotic progression. Cancer Res 65:10872–10880
Acknowledgments
We thank C. Johanet for providing the reagents and P. Coopman for the stimulating discussions. This work was supported by the Association Française contre les Myopathies (AFM), the Ligue Nationale Contre le Cancer (Comités Départementaux de l’Hérault and de l’Aveyron and Comité Régional du Languedoc-Roussillon), and the GEFLUC (Languedoc-Roussillon).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Magnaghi-Jaulin, L., Marcilhac, A., Rossel, M. et al. Calpain 2 is required for sister chromatid cohesion. Chromosoma 119, 267–274 (2010). https://doi.org/10.1007/s00412-010-0255-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00412-010-0255-z