Sensing and repletion mechanisms of calcium stores

抄録

Calcium signaling is a central mechanism involved in neuronal functions and pathological conditions, including chronic pain. Two important and widespread ion channels may contribute to calcium signaling in this context: the Calcium Release-Activated Calcium (CRAC) channels underlying store-operated calcium entry (SOCE) and the Transient Receptor Potential Melastatin 7 (TRPM7) chanzyme, which combines a calcium-permeable ion channel and a kinase domain with phosphotransferase activity. In addition to calcium signaling, both mechanisms may contribute to calcium store refilling. In this presentation, I will discuss how TRPM7 contributes to and interacts with store operated calcium entry (SOCE) and how this affects the store refilling process and the store content in B lymphocytes. We found that although TRPM7 itself is not a store-operated ion channel, its activity is acutely linked to SOCE and its facilitating modulatory effect is mediated the kinase domain of the protein. In addition, TRPM7 contributes to calcium homeostasis by maintaining the filling state of intracellular calcium stores in resting cells, and this effect is mediated by TRPM7's ion channel domain. We hypothesize that TRPM7 channel activity is required to maintain the cellular calcium store content and that TRPM7 kinase phosphorylates and thereby modulates STIM proteins and/or other SOCE components. We conclude that the channel kinase TRPM7 and SOCE are synergistic mechanisms regulating intracellular calcium homeostasis.