| Literature DB >> 26321635 |
Kiyoto Kurima1, Seham Ebrahim2, Bifeng Pan3, Miloslav Sedlacek2, Prabuddha Sengupta4, Bryan A Millis2, Runjia Cui2, Hiroshi Nakanishi1, Taro Fujikawa2, Yoshiyuki Kawashima1, Byung Yoon Choi1, Kelly Monahan1, Jeffrey R Holt3, Andrew J Griffith5, Bechara Kachar6.
Abstract
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.Entities:
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Year: 2015 PMID： 26321635 PMCID： PMC4569002 DOI： 10.1016/j.celrep.2015.07.058
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423