ABC1, AN ATP BINDING CASSETTE TRANSPORTER REQUIRED FOR PHAGOCYTOSIS OF APOPTOTIC CELLS, GENERATES A REGULATED ANION FLUX AFTER EXPRESSION IN XENOPUS-LAEVIS OOCYTES

The ATP binding cassette transporter ABC1 is a 220-kDa glycoprotein ex pressed by macrophages and required for engulfment of cells undergoing programmed cell death. Since members of this family of proteins such as P-glycoprotein and cystic fibrosis transmembrane conductance regula tor share the ability to transport anions, we have investigated the tr ansport capability of ABC1 expressed in Xenopus oocytes using iodide e fflux and voltage-clamp techniques. We report here that ABC1 generates an anion flux sensitive to glibenclamide, sulfobromophthalein, and bl ockers of anion transporters. The anion flux generated by ABC1 is upre gulated by orthovanadate, cAMP, protein kinase A, and okadaic acid. In other ABC transporters, mutating the conserved lysine in the nucleoti de binding folds was found to severely reduce or abolish hydrolysis of ATP, which in turn altered the activity of the transporter. In ABC1, replacement of the conserved lysine 1892 in the Walker A motif of the second nucleotide binding fold increased the basal ionic flux, did not alter the pharmacological inhibitory profile, but abolished the respo nse to orthovanadate and cAMP agonists. Therefore, we conclude that AB C1 is a cAMP-dependent and sulfonylurea-sensitive anion transporter.