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Tricellulin is a tight-junction protein necessary for hearing.

The inner ear has fluid-filled compartments of different ionic compositions, including the endolymphatic and perilymphatic spaces of the organ of Corti; the separation from one another by epithelial barriers is required for normal hearing. TRIC encodes tricellulin, a recently discovered tight-junction (TJ) protein that contributes to the structure and function of tricellular contacts of neighboring cells in many epithelial tissues. We show that, in humans, four different recessive mutations of TRIC cause nonsyndromic deafness (DFNB49), a surprisingly limited phenotype, given the widespread tissue distribution of tricellulin in epithelial cells. In the inner ear, tricellulin is concentrated at the tricellular TJs in cochlear and vestibular epithelia, including the structurally complex and extensive junctions between supporting and hair cells. We also demonstrate that there are multiple alternatively spliced isoforms of TRIC in various tissues and that mutations of TRIC associated with hearing loss remove all or most of a conserved region in the cytosolic domain that binds to the cytosolic scaffolding protein ZO-1. A wild-type isoform of tricellulin, which lacks this conserved region, is unaffected by the mutant alleles and is hypothesized to be sufficient for structural and functional integrity of epithelial barriers outside the inner ear.

Pubmed ID: 17186462 RIS Download

Mesh terms: Alternative Splicing | Amino Acid Sequence | Animals | Cytosol | Ear, Inner | Epithelial Cells | Female | Hearing | Hearing Loss | Humans | Intercellular Junctions | MARVEL Domain Containing 2 Protein | Male | Membrane Proteins | Mice | Mice, Inbred C57BL | Molecular Sequence Data | Mutation | Occludin | Organ of Corti | Pedigree | Phosphoproteins | Protein Isoforms | Sequence Homology, Amino Acid | Zonula Occludens-1 Protein

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK61397
  • Agency: NIDCD NIH HHS, Id: Z01 DC000039-08
  • Agency: NIDCD NIH HHS, Id: Z01 DC000039
  • Agency: NIDCD NIH HHS, Id: Z01 DC000035-08
  • Agency: NIDDK NIH HHS, Id: R56 DK061397
  • Agency: Intramural NIH HHS, Id: T32 DC000035
  • Agency: NIDCD NIH HHS, Id: R01 DK061397
  • Agency: NIDDK NIH HHS, Id:
  • Agency: Wellcome Trust, Id:

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NIH genetic sequence database that provides an annotated collection of all publicly available DNA sequences for almost 280 000 formally described species. (Jan 2014) These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of the International Nucleotide Sequence Database Collaboration and daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP.


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