Electrodiffusional ATP movement through CFTR and other ABC transporters

The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the superfamily of ATP-binding cassette (ABC) transporters, also known a s traffic ATPases. Recent studies from our laboratory determined that vario us members of the ABC family of transport proteins mediate the electrodiffu sional movement of the nucleotide ATR In this report, evidence for the move ment of cellular nucleotides by the ABC transporter CFTR and related molecu les, including P-glycoproteins (Pgp), is reviewed. The wild-type mdr1 gene product, Pgp, enables the spontaneous release of cellular ATP. However, sin gle amino acid substitutions in both nucleotide-binding sites render a dysf unctional Pgp, whose function can only be reversed by voltage activation. T his report includes data indicating that reconstitution of highly purified CFTR from human epithelial origin enables the permeation of both Cl and ATR The relevance of the ABC domains in ATP transport is also explored, and th e hypothesis is forwarded that improper ATP transport by a dysfunctional CF TR is a relevant factor in cystic fibrosis.