REGULATION OF CFTR CHLORIDE CHANNELS BY SYNTAXIN AND MUNC18 ISOFORMS

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(1-4). The molecular mechanisms that m odulate CFTR activity in epithelial tissues are poorly understood, Her e we show that CFTR is regulated by an epithelially expressed syntaxin (syntaxin 1A), a membrane protein that also modulates neurosecretion( 5-7) and calcium-channel gatings(8-11) in brain, Syntaxin 1A physicall y interacts with CFTR chloride channels and regulates CFTR-mediated cu rrents both in Xenopus oocytes and in epithelial cells that normally e xpress these proteins. The physical and functional interactions betwee n syntaxin 1A and CFTR are blocked by a syntaxin-binding protein of th e Munc18 protein family (also called n-Sec1; refs 12-14). Our results indicate that CFTR function in epithelial cells is regulated by an int erplay between syntaxin and Munc18 isoforms.