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 (α, β and γ) with several splice variants have been found to date. In the present paper, we describe the discovery of a novel splice variant of the γ isoform, which we call PIPkin Iγc, 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 Iγc in rat cerebellar granule cells causes a progressive loss of their neuronal processes, whereas equivalent kinase-dead versions of PIPkin Iγa did not induce any such effect, suggesting the possible existence of a specific PtdIns(4,5)P2 pool synthesized by PIPkin Iγc, which is involved in the maintenance of some neuronal cellular processes.

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