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

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.