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Members of the thrombospondin gene family bind stromal interaction molecule 1 and regulate calcium channel activity

By Mark Duquette, Monica Nadler, Dayne Okuhara, Jill Thompson, Trevor Shuttleworth and Jack Lawler

Abstract

The thrombospondins (TSPs) are a family of matricellular proteins that regulate cellular phenotype through interactions with a myriad of other proteins and proteoglycans. We have identified a novel interaction of the members of the TSP gene family with stromal interaction molecule 1 (STIM1). This association is robust since it is preserved in Triton X-100, can be detected with multiple anti-TSP-1 and anti-STIM1 antibodies, and is detected in a wide range of cell types. We have also found that STIM1 co-immunoprecipitates with TSP-4 and cartilage oligomeric matrix protein (COMP), and that a recombinant version of the N-terminal domain of STIM1 binds to the signature domain of TSP-1 and COMP. The association of the TSPs with STIM1 is observed in both the presence and absence of calcium indicating that the calcium-dependent conformation of the signature domain of TSPs is not required for binding. Thus, this interaction could occur in the ER under conditions of normal or low calcium concentration. Furthermore, we observed that the expression of COMP in HEK 293 cells decreases STIM1-mediated calcium release activated calcium (CRAC) channel currents and increases arachidonic acid calcium (ARC) channel currents. These data indicate that the TSPs regulate STIM1 function and participate in the reciprocal regulation of two channels that mediate calcium entry into the cell

Topics: Thrombospondin, Stromal interaction molecule 1, Calcium signaling, Arachidonate-regulated calcium channel
Publisher: 'Elsevier BV'
Year: 2015
DOI identifier: 10.1016/j.matbio.2014.05.004.
OAI identifier: oai:dash.harvard.edu:1/17820894
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