title: Comparative phenotypic analysis of the two major splice isoforms of phosphatidylinositol phosphate kinase type Iγ in vivo.
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 Iγ (PIPKIγ), encoded by the gene Pip5k1c, versus ablation of a specific splice isoform, PIPKIγ_i2, with respect to three reported PIPKIγ functions. Ablation of PIPKIγ_i2 caused a neuron-specific endocytosis defect similar to that found in PIPKIγ(-/-) mice, while agonist-induced calcium signaling was reduced in PIPKIγ(-/-) cells, but was not affected in the absence of PIPKIγ_i2. A reported contribution of PIPKIγ to epithelial integrity was not evident in PIPKIγ(-/-) mice. Given that mice lacking PIPKIγ_i2 live a normal lifespan whereas PIPKIγ(-/-) mice die shortly after birth, we propose that PIPKIγ-mediated metabotropic calcium signaling may represent an essential function of PIPKIγ, whereas functions specific to the PIPKIγ_i2 splice isoform are not essential for survival.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried,  82152 Germany.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Legate
authors.forename: Dirk
authors.initials: D
authors.lastname: Montag
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Böttcher
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018129:Phosphatidylinositol Phosphates; D020033:Protein Isoforms; D017853:Phosphotransferases (Alcohol Group Acceptor)