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Calumenin but not reticulocalbin forms a Ca2+-dependent complex with thrombospondin-1. A potential role in haemostasis and thrombosis

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Abstract

Thrombocytes express thrombospondin-1 (TSP1), as well as the CREC proteins, calumenin and reticulocalbin. TSP1 and calumenin are released upon stimulation with thrombin. Calumenin has recently been shown to influence the synthesis of certain coagulation factors. Calumenin is present in atherosclerotic lesions but not in normal vasculature [Coppinger et al. (Blood 103:2096–2104, 2004)] and is able to modulate the protein expression pattern as well as the cell cycle of fibroblasts [Østergaard et al. (Proteomics 6:3509–3519, 2006)]. We here show that calumenin in the presence of Ca2+ binds to TSP1 with a dissociation constant K d around 0.4 μM. This interaction is specific with respect to the secreted calumenin as the closest relative among the CREC family members, the non-secreted reticulocalbin, does not form a similar complex. This further indicates that calumenin may be broadly involved in haemostasis and in the pathophysiology of thrombosis.

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Acknowledgements

We thank Dr. Ozawa for the kind gift of the pGEX vector containing reticulocalbin. We thank Inge Kjærgaard, Kirsten Peterslund and Anne Marie Bundsgaard for expert technical assistance. This study was supported by research funding from the Danish Medical Research Council, the John and Birthe Meyer Foundation, the Danish Cancer Foundation and Aarhus University Research Foundation.

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  1. Institute of Medical Biochemistry, University of Aarhus, Ole Worms Allé, Building 1170, 8000, Aarhus C, Denmark

    Gry Aune Westergaard Hansen, Henrik Vorum, Christian Jacobsen & Bent Honoré

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  1. Gry Aune Westergaard Hansen
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Correspondence to Bent Honoré.

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Hansen, G.A.W., Vorum, H., Jacobsen, C. et al. Calumenin but not reticulocalbin forms a Ca2+-dependent complex with thrombospondin-1. A potential role in haemostasis and thrombosis. Mol Cell Biochem 320, 25–33 (2009). https://doi.org/10.1007/s11010-008-9895-1

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