Functional properties of a pore mutant in the Drosophila melanogaster inositol 1,4, 5-trisphosphate receptor

Abstract

The inositol (1,4,5)-trisphosphate receptor (InsP₃R) is an intracellular calcium release channel that plays a crucial role in cell signaling. In Drosophila melanogaster, a single InsP₃R gene (itpr) encodes a protein (DmInsP₃R) that is ~60% conserved with mammalian InsP₃Rs. The functional properties of wild-type (WT) and mutant DmInsP₃Rs have recently been described [Srikanth et al., Biophys. J. 86 (2004) 3634-3646]. Here, we use the planar lipid bilayer reconstitution technique to describe single channel properties of a ka901 point mutant (G2630S) in the pore-forming region of DmInsP₃R. We find that homomeric ka901 channels are not functional, but the heteromeric WT:ka901 mutant channels display increased conductance, longer channel open time and altered ion selectivity properties when compared to WT DmInsP₃R. Obtained results are consistent with the gain of function phenotype observed in ka901/+ mutant flies.