Junctional membrane-targeting mechanism of cardiac L-type calcium channel

在心肌细胞中，L型钙通道（LTCC）与连接膜（JM）上的兰尼碱受体形成功能性信号复合物。尽管LTCCs在JM上的特异性定位对于兴奋-收缩偶联至关重要，但其靶向机制尚不清楚。为了鉴定负责JM靶向的a_的序列<1C>，我们产生了aic亚基的各种突变体，并研究了它们在非基因型（a_&lt;1 S. null）GLT肌管。结果显示，<1681><1688><1693><1700>预测在近端C-末端形成两个相邻α-螺旋的氨基酸LQAGLRTL^和PEIRRAIS^对于α-的JM-靶向是必需的<1C>。

In cardiac myocytes, L-type calcium channels(LTCC) form a functional signaling complex with ryanodine receptors at the junctional membrane(JM). Although the specific localization of LTCCs to JM is critical for excitation-contraction coupling, their targeting mechanism is unclear. To identify the sequences of a_<1C> responsible for the JM-targeting, we generated various mutants of aic subunit, and studied their targeting properties in dysgenic(a_<1S.-null) GLT myotubes. The results revealed that amino acids^<1681> LQAGLRTL^<1688> and^<1693> PEIRRAIS^<1700> predicted to form two adjacent a-helices in the proximal C-terminus are necessary for the JM-targeting of a_<1C>.