Na+/Ca2+ exchanger in Drosophila: Cloning, expression, and transport differences

cDNAs for the Na+/Ca2+ exchanger from Drosophila melanogaster (Dmel/Ncx) have been cloned by homology screening using the human heart Na+/Ca2+ exchanger cDNA. The overall deduced protein structure for Dmel/Ncx is similar to that of mammalian Na+/Ca2+ exchanger genes NCX1 and NCX2, having six hydrophobic regions in the amino terminus separated from six at the carboxy-terminal end by a large intracellular loop. Sequence comparison of the Drosophila exchanger cDNAs with NCX1 and NCX2 Na+/Ca2+ exchangers are similar to 46% identical at the deduced amino acid level. Consensus phosphorylation sites for both protein kinase C and protein kinase A are present on the intracellular loop region of the Dmel/Ncx. Alternative splicing for the Dmel/Ncx gene is suggested in the same intracellular loop region as demonstrated for NCX1. Functionally, the Drosophila Na+/Ca2+ exchanger expressed in oocytes differs from expressed mammalian NCX1 with regard to Ca2+ transport in Ca2+/Ca2+ exchange and the effect of monovalent-dependent Ca2+/Ca2+ exchange. The Dmel/Ncx gene maps to chromosome 3 (93A-B) using in situ hybridization to polytene chromosomes, the same position as the Na+-K+-ATPase, a related transporter. We conclude that, although extracellular Na+ concentration-dependent Ca2+ transport is subserved by both human and Drosophila Na+/Ca2+ exchangers, there are clear and important differences in the transporters, which should be useful in deducing how the Na+/Ca2+ exchanger protein function depends on its structure.