Expression of AE3 cDNA in COS cells led to chronic cytoplasmic acidification and chloride- and bicarbonate-dependent changes in intracellular pH, confirming its function as an anion exchanger.
We have isolated AE3, a novel gene expressed primarily in brain neurons and in heart. The predicted AE3 polypeptide shares a high degree of identity with the anion exchange and cytoskeletal binding domains of the erythrocyte band 3 protein. Expression of AE3 cDNA in COS cells leads to chronic cytoplasmic acidification and to chloride- and bicarbonate-dependent changes in intracellular pH, confirming that this gene product is an anion exchanger. Characterization of an AE3 mutant lacking the NH2-terminal 645 amino acids demonstrates that the COOH-terminal half of the polypeptide is both necessary and sufficient for correct insertion into the plasma membrane and for anion exchange activity. The NH2-terminal domain may play a role in regulating the activity of the exchanger and may be involved in the structural organization of the cytoskeleton in neurons.
Kopito et al. (1989) studied this question. Expression of AE3 cDNA vs. AE3 mutant lacking NH2-terminal 645 amino acids was evaluated on Intracellular pH regulation and anion exchange activity. Expression of AE3 cDNA in COS cells led to chronic cytoplasmic acidification and chloride- and bicarbonate-dependent changes in intracellular pH, confirming its function as an anion exchanger.