Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition (Articolo in rivista)

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  • Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1073/pnas.1211869109 (literal)
Alternative label
  • Rodriguez, Laura; Simeonato, Elena; Scimemi, Pietro; Anselmi, Fabio; Cali, Bianca; Crispino, Giulia; Ciubotaru, Catalin D.; Bortolozzi, Mario; Ramirez, Fabian Galindo; Majumder, Paromita; Arslan, Edoardo; De Camilli, Pietro; Pozzan, Tullio; Mammano, Fabio (2012)
    Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition
    in Proceedings of the National Academy of Sciences of the United States of America
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Rodriguez, Laura; Simeonato, Elena; Scimemi, Pietro; Anselmi, Fabio; Cali, Bianca; Crispino, Giulia; Ciubotaru, Catalin D.; Bortolozzi, Mario; Ramirez, Fabian Galindo; Majumder, Paromita; Arslan, Edoardo; De Camilli, Pietro; Pozzan, Tullio; Mammano, Fabio (literal)
Pagina inizio
  • 14013 (literal)
Pagina fine
  • 14018 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.ncbi.nlm.nih.gov/pubmed/22891314 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 109 (literal)
Rivista
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  • 6 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 35 (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Fdn Ric Biomed Avanzata; University of Padua; University of Padua; University of Padua; University of Padua; Osped Ca Foncello; Consorzio Interuniv Nazl Sci & Tecnol Mat; Howard Hughes Medical Institute; Yale University; Yale University; Consiglio Nazionale delle Ricerche (CNR) (literal)
Titolo
  • Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition (literal)
Abstract
  • Phosphatidylinositol phosphate kinase type 1 gamma (PIPKI gamma) 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 PIPKI gamma(+/-) siblings breed normally and have no reported phenotype. Here we show that adult PIPKI gamma(+/-) mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca2+ signaling activity in cochlear nonsensory cells. Because Ca2+ 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) PIPKI gamma 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 PIPKI gamma(+/-) mice. This mouse model also suggests that PIPKI gamma may determine the level of gap junction contribution to cochlear development. (literal)
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