Comparative phenotypic analysis of the two major splice isoforms of phosphatidylinositol phosphate kinase type Iγ in vivo

Localized production of polyphosphoinositides is critical for their signaling function. To examine the biological relevance of specific pools of phosphatidylinositol 4,5-bisphosphate we compared the consequences of genetically ablating all isoforms of phosphatidylinositol phosphate (PIP) kinase type I gamma (PIPKI gamma), encoded by the gene Pip5k1c, versus ablation of a specific splice isoform, PIPKI gamma_i2, with respect to three reported PIPKI gamma functions. Ablation of PIPKI gamma_i2 caused a neuron-specific endocytosis defect similar to that found in PIPKI gamma(-/-) mice, while agonist-induced calcium signaling was reduced in PIPKI gamma(-/-) cells, but was not affected in the absence of PIPKI gamma_i2. A reported contribution of PIPKI gamma to epithelial integrity was not evident in PIPKI gamma(-/-) mice. Given that mice lacking PIPKI gamma_i2 live a normal lifespan whereas PIPKI gamma(-/-) mice die shortly after birth, we propose that PIPKI gamma-mediated metabotropic calcium signaling may represent an essential function of PIPKI gamma, whereas functions specific to the PIPKI gamma_i2 splice isoform are not essential for survival.