IP3 Receptor-Dependent Cytoplasmic Ca2+ Signals Are Tightly Controlled by Cavβ3
IP3 Receptor-Dependent Cytoplasmic Ca2+ Signals Are Tightly Controlled by Cavβ3
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DOI：
10.1016/j.celrep.2018.01.010
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发表时间：
2018-01-30
期刊：
影响因子：
8.8
通讯作者：
Flockerzi, Veit
中科院分区：
文献类型：
--
作者：
Belkacemi, Anouar;Hui, Xin;Flockerzi, Veit
电压门控钙通道（Cavs）是可兴奋细胞中主要的钙离子进入途径。它们的β亚基促进通道的离子传导α 1孔的膜运输并调节其门控特性。我们报告说，一个B亚基，β 3，减少钙释放后，刺激磷脂酶C偶联受体和肌醇1，4，5-三磷酸（IP 3）的形成。这种作用需要Cav β 3的SH 3-HOOK结构域，包括物理β 3/IP 3受体相互作用，并且当激动剂诱导的IP 3形成被笼状IP 3的光解绕过时占优势。与β 3作为Ca 2+释放的制动器一致，成纤维细胞迁移在体外增强，并且在体内，在β 3不存在的情况下，皮肤伤口的闭合加速。为了介导特定的生理反应并防止Ca 2+毒性，必须严格控制胞质Ca 2+信号。所描述的β 3的功能，与其作为Cav亚基的功能无关，增加了这种严格的控制。
Voltage-gated calcium channels (Cavs) are major Ca2+ entry pathways in excitable cells. Their beta subunits facilitate membrane trafficking of the channel's ion-conducting alpha 1 pore and modulate its gating properties. We report that one b subunit, beta 3, reduces Ca2+ release following stimulation of phospholipase C-coupled receptors and inositol 1,4,5-trisphosphate (IP3) formation. This effect requires the SH3-HOOK domain of Cav beta 3, includes physical beta 3/IP3 receptor interaction, and prevails when agonist-induced IP3 formation is bypassed by photolysis of caged IP3. In agreement with beta 3 acting as a brake on Ca2+ release, fibroblast migration is enhanced in vitro, and in vivo, closure of skin wounds is accelerated in the absence of beta 3. To mediate specific physiological responses and to prevent Ca2+ toxicity, cytoplasmic Ca2+ signals must be tightly controlled. The described function of beta 3, unrelated to its function as a Cav subunit, adds to this tight control.