GENERATION OF TRUNCATED BRAIN AE3 ISOFORMS BY ALTERNATE MESSENGER-RNA PROCESSING

AE3 gene is a member of the AE anion exchanger gene family that is expressed primarily in brain and heart. The principal product of the AE3 gene in rodent brain, FL-AE3p, when expressed in heterologous cell lines, gives rise to chloride-dependent changes in intracellular pH consistent with its operation as an anion exchanger. We have identified two novel isoforms of mouse AE3 that are generated by tissue-specific alternate RNA processing. One of these isoforms encodes a polypeptide, 14-AE3p, that corresponds to a portion of the NH2-terminal cytoplasmic domain of AE3. 14-AE3p lacks the entire transmembrane domain that - in FL-AE3p - forms the anion exchange channel. Immunoblots with antibodies to the NH2- and COOH- termini confirm that FL-AE3 and 14-AE3 are expressed in rat brain as 160 kDa and 74 kDa polypeptides, respectively. Unlike FL-AE3p, however, 14-AE3p is insoluble in non-ionic detergent, suggesting a possible association with the cytoskeleton.