Naren A P, Nelson D J, Xie W, Jovov B, Pevsner J, Bennett M K, Benos D J, Quick M W, Kirk K L
Department of Physiology and Biophysics, Gregory Fleming James Cystic Fibrosis Research Center, Birmingham, Alabama 35294, USA.
Nature. 1997 Nov 20;390(6657):302-5. doi: 10.1038/36882.
The cystic fibrosis gene encodes a cyclic AMP-gated chloride channel (CFTR) that mediates electrolyte transport across the luminal surfaces of a variety of epithelial cells. The molecular mechanisms that modulate CFTR activity in epithelial tissues are poorly understood. Here we show that CFTR is regulated by an epithelially expressed syntaxin (syntaxin 1A), a membrane protein that also modulates neurosecretion and calcium-channel gating in brain. Syntaxin 1A physically interacts with CFTR chloride channels and regulates CFTR-mediated currents both in Xenopus oocytes and in epithelial cells that normally express these proteins. The physical and functional interactions between syntaxin 1A and CFTR are blocked by a syntaxin-binding protein of the Munc18 protein family (also called n-Secl). Our results indicate that CFTR function in epithelial cells is regulated by an interplay between syntaxin and Munc18 isoforms.
囊性纤维化基因编码一种环磷酸腺苷门控氯离子通道（CFTR），该通道介导电解质跨多种上皮细胞腔面的转运。目前对调节上皮组织中CFTR活性的分子机制了解甚少。在此我们表明，CFTR受上皮表达的 syntaxin（syntaxin 1A）调节，syntaxin 1A是一种膜蛋白，在大脑中也调节神经分泌和钙通道门控。Syntaxin 1A与CFTR氯离子通道发生物理相互作用，并在非洲爪蟾卵母细胞和正常表达这些蛋白的上皮细胞中调节CFTR介导的电流。Syntaxin 1A与CFTR之间的物理和功能相互作用被Munc18蛋白家族（也称为n - Secl）的一种 syntaxin结合蛋白阻断。我们的结果表明，上皮细胞中CFTR的功能受 syntaxin和Munc18异构体之间相互作用的调节。
