Properties, Structure, and Function of the Solute Carrier 26 Family of Anion Transporters

Abstract

The SLC26 family of anion transporters consists of ten members that display remarkable functional and substrate diversity. Mutations in several members of the family have been identified as causing a variety of human diseases and mouse phenotype when deleted. The family drew the attention and strong interest of epithelial biologists with the identification of the first elusive luminal Cl−/HCO3− exchanger, which turned to be the third member of the family SLC26A3. Later, a fairly quick progress revealed that members of the family transport all halides, NO3−, SO42−, oxalate, and formate among others. Members of the family can be grouped into three subgroups based on substrate selectivity and transport mode, the SO42− transporters SLC26A1 and SLC26A2; the anion exchangers the 2Cl−/1HCO3− SLC26A3, the 1Cl−/1HCO3− SLC26A4, and the 1Cl−/2HCO3− SLC26A6; and the Cl− channels SLC26A7, SLC26A9, and SLC26A11. Another major leap in our understanding of SLC26 activity emerged from the analysis of the bacterial SLC26 homolog crystal structure that revealed the transmembrane architecture of the protein. This chapter discusses structural features, transport properties, and regulation of the transporters that are essential to understand their functions and roles in human diseases.