title: TMC function in hair cell transduction.
abstract: Transmembrane channel-like (TMC) proteins 1 and 2 are necessary for hair cell mechanotransduction but their precise function is controversial. A growing body of evidence supports a direct role for TMC1 and TMC2 as components of the transduction complex. However, a number of important questions remain and alternate hypotheses have been proposed. Here we present an historical overview of the identification and cloning of Tmc genes, a discussion of mutations in TMC1 that cause deafness in mice and humans and a brief review of other members of the Tmc gene superfamily. We also examine expression of Tmc mRNAs and localization of the protein products. The review focuses on potential functions of TMC proteins and the evidence from Beethoven mice that suggests a direct role for TMC1 in hair cell mechanotransduction. Data that support alternate interpretations are also considered. The article concludes with a discussion of outstanding questions and future directions for TMC research. This article is part of a Special Issue entitled <Annual Reviews 2014>.
authors.affiliation: Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: jeffrey.holt@childrens.harvard.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Holt
authors.affiliation: Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bifeng
authors.initials: B
authors.lastname: Pan
authors.affiliation: Program in Neuroscience, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Mounir A
authors.initials: MA
authors.lastname: Koussa
authors.affiliation: Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Asai
mesh_terms: D000161:Acoustic Stimulation; D000595:Amino Acid Sequence; D000818:Animals; D001307:Auditory Perception; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000378:metabolism*; D006309:Hearing; D006311:Hearing Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D040542:Mechanotransduction, Cellular; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data
chemical_list: D008565:Membrane Proteins; C451751:TMC1 protein, human; C575756:TMC2 protein, human