Functional Characterization of Zebrafish Anion Exchanger slc4/a2/ae2.1




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Anion exchangers play a significant role in animal physiology. They maintain homeostasis by regulating cell volume, pH, and intracellular Cl- in a wide range of cells and tissues, including erythrocytes, epithelial renal and gut cells, and neuronal cells. Both human and mouse AE1 anion exchangers are involved in systemic disposal of metabolic CO2 by the circulatory system, while AE2 anion exchangers are involved in regulation of intracellular pH, intracellular [Cl-], and in defending against hypertonic stress. Zebrafish are excellent organisms in which to study the developmental pattern and function of protein expression, but have infrequently been used for the study of ion transport proteins. The purpose of this study is to functionally compare the zebrafish slc4a2 anion exchanger homolog zae2.1 with the related zebrafish anion exchanger zAE2.0 and their mouse ortholog slc4a2/ae2 (mAE2a). This study found that zAE2.1 expressed in Xenopus laevis oocytes mediates electroneutral, Na+-independent, 36Cl-/Cl- exchange. Furthermore, zAE2.1 activity is stimulated by intracellular and extracellular alkalization by the oocyte intracellular acidifier NH4+. zAE2.1 function is inhibited by intracellular and extracellular acidification and by the transport antagonist, 4,4-diisothiocyanatostilbene-2,2-disulfonate (DIDS). These data indicate that zae2.1 functionally resembles zAE2 and mAE2a. These functional data should provide a context for interpretation of ongoing knockdown studies, yielding additional insight into anion exchanger function and development in the zebrafish.



zebrafish anion exchangers, pH, regulation, xenopus, oocytes, ion, transporters