Four novel sequences in Drosophila melanogaster homologous to the auxiliary Para sodium channel subunit TipE

TipE is an auxiliary subunit of the Drosophila Para sodium channel. Here we describe four sequences, TEH1-4, homologous to TipE in the Drosophila melanogaster genome, harboring all typical structures of both TipE and the β-Subunit family of big-conductance Ca2+-activated potassium channels: short cytosolic N- and C-terminal stretches, two transmembrane domains, and a large extracellular loop with two disulfide bonds. Whereas TEH1 and TEH2 lack the TipE-specific extension in the extracellular loop, both TEH3 and TEH4 possess two extracellular EGF-like domains. A CNS-specific expression was found for TEH1, while TEH2-4 were more widely expressed. The genes for TEH2-4 are localized close to the tipE gene on chromosome 3L. Coexpression of TEH subunits with Para in Xenopus oocytes showed a strong (30-fold, TEH1), medium (5- to 10-fold, TEH2 and TEH3), or no (TEH4) increase in sodium current amplitude, while TipE increased the current 20-fold. In addition, steady-state inactivation and the recovery from fast inactivation were altered by coexpression of Para with TEH1. We conclude that members of the TEH-family are auxiliary subunits for Para sodium channels and possibly other ion channels.