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Abstract

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.