| First Author | Rodriguez L | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 35 | Pages | 14013-8 |
| PubMed ID | 22891314 | Mgi Jnum | J:188582 |
| Mgi Id | MGI:5441133 | Doi | 10.1073/pnas.1211869109 |
| Citation | Rodriguez L, et al. (2012) Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition. Proc Natl Acad Sci U S A 109(35):14013-8 |
| abstractText | Phosphatidylinositol phosphate kinase type 1gamma (PIPKIgamma) is a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and is expressed at high levels in the nervous system. Homozygous knockout mice lacking this enzyme die postnatally within 24 h, whereas PIPKIgamma(+/-) siblings breed normally and have no reported phenotype. Here we show that adult PIPKIgamma(+/-) mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca(2+) signaling activity in cochlear nonsensory cells. Because Ca(2+) signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P(2), we conclude that (i) PIPKIgamma is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P(2) pool in the cell syncytia that supports auditory hair cells; (ii) spatially graded impairment of this signaling pathway in cochlear nonsensory cells causes a selective alteration in the acquisition of hearing in PIPKIgamma(+/-) mice. This mouse model also suggests that PIPKIgamma may determine the level of gap junction contribution to cochlear development. |
