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 Dme]/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 ~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.