Characterization of Anopheles gambiae Slc26a5 and potential role in malaria

Abstract

Malaria transmission requires Plasmodium invasion of the Anopheles mosquito midgut. This critical first step involves adhesion to chondroitin sulfate (ChSO4)[Dinglasan et al, PNAS 2007], a midgut epithelial ligand. Sulfate (SO42−) for ChSO4 biosynthesis is supplied by midgut SO42− uptake. Slc26 proteins transport many anions: Cl−, HCO3−, oxalate (ox2−), and SO42−. Recently, we found that Drosophila Slc26a5 is an electrogenic Cl−/SO42−, Cl−/ox2− and Cl−/nHCO3− exchanger [Hirata et al, JASN 2009], and SO42− transport exceeded ox2− transport. Therefore we searched EST and genomic databases to identify two Slc26a5 orthologues (AgSlc26a5A and ‐B). We expressed AgSlc26a5A and B in Xenopus oocytes to evaluate transport using microelectrodes. AgSlc26a5A is found in the salivary glands and gastric caeca. However, AgSlc26a5A did not obviously transport Cl−, HCO3−, SO42− or ox2−. On the other hand, AgSlc26a5B has transport properties similar to mouse Slc26a6 and Drosophila Slc26a5. That is, AgSlc26a5B mediates electrogenic Cl−/SO42−, Cl−/ox2− and Cl−/nHCO3− exchange. And, AgSlc26a5B is enriched in the hindgut (including Malpighian tubules) and the posterior midgut. These results suggest that AgSlc26a5B can alkalinize the Anopheles midgut and is also a candidate for SO42− supplier to midgut cell. Thus, we hypothesize that control of AgSlc26a5B activity could control parasite (Plasmodium) invasion.