Lesage F, Hibino H, Hudspeth A J
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):671-5. doi: 10.1073/pnas.0307681100. Epub 2003 Dec 30.
The association of Ca(2+)-activated K(+) channels with voltage-gated Ca(2+) channels at the presynaptic active zones of hair cells, photoreceptors, and neurons contributes to rapid repolarization of the membrane after excitation. Ca(2+) channels have been shown to bind to a large set of synaptic proteins, but the proteins interacting with Ca(2+)-activated K(+) channels remain unknown. Here, we report that the large-conductance Ca(2+)-activated K(+) channel of the chicken's cochlear hair cell interacts with beta-catenin. Yeast two-hybrid assays identified the S10 region of the K(+) channel's alpha-subunit and the ninth armadillo repeat and carboxyl terminus of beta-catenin as necessary for the interaction. An antiserum directed against the alpha-subunit specifically coprecipitated beta-catenin from brain synaptic proteins. beta-Catenin is known to associate with the synaptic protein Lin7/Velis/MALS, whose interaction partner Lin2/CASK also binds voltage-gated Ca(2+) channels. beta-Catenin may therefore provide a physical link between the two types of channels at the presynaptic active zone.
在毛细胞、光感受器和神经元的突触前活动区,钙激活钾通道与电压门控钙通道的结合有助于兴奋后膜的快速复极化。钙通道已被证明能与大量突触蛋白结合,但与钙激活钾通道相互作用的蛋白仍不清楚。在此,我们报告鸡耳蜗毛细胞的大电导钙激活钾通道与β-连环蛋白相互作用。酵母双杂交试验确定钾通道α亚基的S10区域以及β-连环蛋白的第九个犰狳重复序列和羧基末端是这种相互作用所必需的。一种针对α亚基的抗血清能从脑突触蛋白中特异性共沉淀β-连环蛋白。已知β-连环蛋白与突触蛋白Lin7/Velis/MALS相关联,其相互作用伴侣Lin2/CASK也与电压门控钙通道结合。因此,β-连环蛋白可能在突触前活动区的两种通道之间提供物理连接。