CFTR - DOMAINS, STRUCTURE, AND FUNCTION

Mutations in the gene encoding the cystic fibrosis transmembrane condu ctance regulator (CFTR) cause cystic fibrosis (CF) (Collins, 1992). Ov er 500 naturally occurring mutations have been identified in CF gene w hich are located in all of the domains of the protein (Kerem et al., 1 990; Mercier et at, 1993; Ghanem et al., 1994; Fanen et at, 1992; Fere c et at, 1992; Cutting et at, 1990). Early studies by several investig ators characterized CFTR as a chloride channel (Anderson et al.; 1991b ,c; Bear et at, 1991). The complex secondary structure of the protein suggested that CFTR might possess other functions in addition to being a chloride channel. Studies have established that the CFTR functions not only as a chloride channel but is indeed a regulator of sodium cha nnels (Stuns ct at, 1995), outwardly rectifying chloride channels (ORC C) (Gray et at, 1989; Garber et al., 1992; Egan et al., 1992; Hwang et at, 1989; Schwiebert et al., 1995) and also the transport of ATP (Sch wiebert et al., 1995; Reisin et at, 1994). This mini-review deals with the studies which elucidate the functions of the various domains of C FTR, namely the transmembrane domains, TMD1 and TMD2, the two cytoplas mic nucleotide binding domains, NBD1 and NBD2, and the regulatory, R, domain.