A novel neuronal-specific splice variant of Type I phosphatidylinositol 4-phosphate 5-kinase isoform gamma.

Abstract

Type I PIPkins (phosphatidylinositol 4-phosphate 5-kinases) are the enzymes that catalyse the major cellular route of synthesis of PtdIns(4,5) P2, and three isoforms (alpha, beta and gamma) with several splice variants have been found to date. In the present paper, we describe the discovery of a novel splice variant of the gamma isoform, which we call PIPkin Igammac, and which is characterized by the inclusion of a 26-amino-acid insert near the C-terminus. Its transcript appears to be selectively expressed in brain, where it locates in the neurons of restricted regions, such as cerebellum, hippocampus, cortex and olfactory bulb, as indicated by in situ hybridization studies. Overexpression of two different catalytically inactive constructs of PIPkin Igammac in rat cerebellar granule cells causes a progressive loss of their neuronal processes, whereas equivalent kinase-dead versions of PIPkin Igammaa did not induce any such effect, suggesting the possible existence of a specific PtdIns(4,5) P2 pool synthesized by PIPkin Igammac, which is involved in the maintenance of some neuronal cellular processes.