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TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia.
Kurima, Kiyoto; Ebrahim, Seham; Pan, Bifeng; Sedlacek, Miloslav; Sengupta, Prabuddha; Millis, Bryan A; Cui, Runjia; Nakanishi, Hiroshi; Fujikawa, Taro; Kawashima, Yoshiyuki; Choi, Byung Yoon; Monahan, Kelly; Holt, Jeffrey R; Griffith, Andrew J; Kachar, Bechara.
Afiliação
  • Kurima K; Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Ebrahim S; Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Pan B; Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Sedlacek M; Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Sengupta P; Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
  • Millis BA; Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Cui R; Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Nakanishi H; Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Fujikawa T; Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Kawashima Y; Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Choi BY; Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Monahan K; Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
  • Holt JR; Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Griffith AJ; Molecular Biology and Genetics Section, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA,. Electronic address: griffita@nidcd.nih.gov.
  • Kachar B; Laboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA,. Electronic address: kacharb@nidcd.nih.gov.
Cell Rep ; 12(10): 1606-17, 2015 Sep 08.
Article em En | MEDLINE | ID: mdl-26321635
Mechanosensitive ion channels at stereocilia tips mediate mechanoelectrical transduction (MET) in inner ear sensory hair cells. Transmembrane channel-like 1 and 2 (TMC1 and TMC2) are essential for MET and are hypothesized to be components of the MET complex, but evidence for their predicted spatiotemporal localization in stereocilia is lacking. Here, we determine the stereocilia localization of the TMC proteins in mice expressing TMC1-mCherry and TMC2-AcGFP. Functionality of the tagged proteins was verified by transgenic rescue of MET currents and hearing in Tmc1(Δ/Δ);Tmc2(Δ/Δ) mice. TMC1-mCherry and TMC2-AcGFP localize along the length of immature stereocilia. However, as hair cells develop, the two proteins localize predominantly to stereocilia tips. Both TMCs are absent from the tips of the tallest stereocilia, where MET activity is not detectable. This distribution was confirmed for the endogenous proteins by immunofluorescence. These data are consistent with TMC1 and TMC2 being components of the stereocilia MET channel complex.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cílios / Células Ciliadas Auditivas Internas / Proteínas de Membrana Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cílios / Células Ciliadas Auditivas Internas / Proteínas de Membrana Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article