细胞内钙信号与平滑肌细胞增殖及去分化

作为内质网膜上的钙感受器，STIM蛋白(包括STIM1及STIM2）会感受内质网内钙水平的降低,结合并激活细胞膜上钙离子通道，Orai1。对STIM1的生理功能以及其耦合并激活Orai1的分子机制的研究一直是个前沿热点领域。但目前对STIM1在平滑肌细胞增殖及表型变化中作用的分子机制还不很清楚,对其同源蛋白STIM2的了解也不多。我们以前的工作表明STIM1在激活Orai1的同时还会耦合抑制L型钙通道。STIM2和L型钙通道在平滑肌内大量存在，他们在上述细胞变化过程中的作用还不清楚。因此本工作的目的是研究1）STIM1，特别是STIM2激活及与它们的靶蛋白（Orai1，特别是LTCC）的相互作用的分子机理；2）STIM和LTCC在平滑肌增殖和表型变化中的作用。我们的研究将提高领域内对内对STIM-Orai1耦合机制的理解，并进一步探索平滑肌损伤修复的机理。

As Calcium sensors on ER membrane, STIM protein will activate calcium channel, Orai1, when ER calcium level is low. The molecular mechanism through which STIM1 couples and activate Orai1 is now a very hot frontier in scientific research. Even though much is known about the structure, function and its coupling with Orai1, little is clear to its homolog, SITM2. Another hot field of research is exploring the physiological roles of STIM. Studies have shown that STIM1 is very important for the proliferation and phenotype switch of smooth muscle cells (SMC). However, the underlying molecular mechanism still remain largely elusive. Our previous work has shown that STIM, while activating Orai1, also can simultaneously inhibit the functionof L-type calcium channel (LTCC). Both LTCC and STIM2 are expressed in SMC, yet their roles in the proliferation and phenotype switch of SMCs are still not very clear. Thus, the current aims of our research are: examine the molecular mechanism by which STIM1, especially STIM2, couple and regulate the function of their target proteins (Orai1, especially LTCC). How STIM proteins and LTCC function during proliferation and phenotype switch of SMCs. Our study will sure improve current understanding on the molecular mechanisms by which STIM1, especially STIM2, couple with their targets and then alter their function. Also, our research will help us understand the mechanisms for the damage-repair of SMCs.