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The solute carrier 26 (SLC26) transporters are anion transporters with diverse substrate specificity. Several members are ubiquitous while others show limited tissue distribution. They are expressed in many epithelia and to the extent known, play a central role in anion secretion and absorption. Members of the family are primarily Cl- transporters, although some members transport mainly SO(4)2-, Cl-, HCO(3)- or I-. A defining feature of the family is their functional diversity. Slc26a1 and Slc26a2 function as specific SO(4)2- transporters while Slc26a4 functions as an electroneutral Cl-/I-/HCO(3)- exchanger. Slc26a3 and Slc26a6 function as coupled electrogenic Cl-/HCO(3)- exchangers or as bona fide anion channels. SLC26A7 and SLC26A9 function exclusively as Cl- channels. This short review discusses the functional diversity of the SLC26 transporters.

The widely expressed anion exchanger polypeptide AE2/SLC4A2 is acutely inhibited by acidic intracellular (pH(i)), by acidic extracellular pH (pH(o)), and by the calmodulin inhibitor, calmidazolium, whereas it is acutely activated by NH(4)(+). The homologous erythroid/kidney AE1/SLC4A1 polypeptide is insensitive to these regulators. Each of these AE2 regulatory responses requires the presence of AE2's C-terminal transmembrane domain (TMD). We have now measured (36)Cl(-) efflux from Xenopus oocytes expressing bi- or tripartite AE2-AE1 chimeras to define TMD subregions in which AE2-specific sequences contribute to acute regulation. The chimeric AE polypeptides were all functional at pH(o) 7.4, with the sole exception of AE2((1-920))/AE1((613-811))/AE2((1120-1237)). Reciprocal exchanges of the large third extracellular loops were without effect. AE2 regulation by pH(i), pH(o) and NH(4)(+) was retained after substitution of C-terminal AE2 amino acids 1120-1237 (including the putative second re-entrant loop, two TM spans and the cytoplasmic tail) with the corresponding AE1 sequence. In contrast, the presence of this AE2 C-terminal sequence was both necessary and sufficient for inhibition by calmidazolium. All other tested TMD substitutions abolished AE2 pH(i) sensitivity, abolished or severely attenuated sensitivity to pH(o) and removed sensitivity to NH(4)(+). Loss of AE2 pH(i) sensitivity was not rescued by co-expression of a complementary AE2 sequence within separate full-length chimeras or AE2 subdomains. Thus, normal regulation of AE2 by pH and other ligands requires AE2-specific sequence from most regions of the AE2 TMD, with the exceptions of the third extracellular loop and a short C-terminal sequence. We conclude that the individual TMD amino acid residues previously identified as influencing acute regulation of AE2 exert that influence within a regulatory structure requiring essential contributions from multiple regions of the AE2 TMD.

Prestin, a member of the solute carrier (SLC) family SLC26A, is the molecular motor that drives the somatic electromotility of mammalian outer hair cells (OHCs). Its closest reported homologue, zebrafish prestin (zprestin), shares approximately 70% strong amino acid sequence similarity with mammalian prestin, predicting an almost identical protein structure. Immunohistochemical analysis now shows that zprestin is expressed in hair cells of the zebrafish ear. Similar to mammalian prestin, heterologously expressed zprestin is found to generate voltage-dependent charge movements, giving rise to a non-linear capacitance (NLC) of the cell membrane. Compared with mammalian prestin, charge movements mediated by zprestin display a weaker voltage dependence and slower kinetics; they occur at more positive membrane voltages, and are not associated with electromotile responses. Given this functional dissociation of NLC and electromotility and the structural similarity with mammalian prestin, we anticipate that zprestin provides a valuable tool for tracing the molecular and evolutionary bases of prestin motor function.