Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with alpha-tectorin and is mutated in autosomal dominant hearing loss (DFNA4)

Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4218-23. doi: 10.1073/pnas.1005842108. Epub 2011 Feb 22.

Abstract

We report on a secreted protein found in mammalian cochlear outer hair cells (OHC) that is a member of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family of adhesion proteins. Ceacam16 mRNA is expressed in OHC, and its protein product localizes to the tips of the tallest stereocilia and the tectorial membrane (TM). This specific localization suggests a role in maintaining the integrity of the TM as well as in the connection between the OHC stereocilia and TM, a linkage essential for mechanical amplification. In agreement with this role, CEACAM16 colocalizes and coimmunoprecipitates with the TM protein α-tectorin. In addition, we show that mutation of CEACAM16 leads to autosomal dominant nonsyndromic deafness (ADNSHL) at the autosomal dominant hearing loss (DFNA4) locus. In aggregate, these data identify CEACAM16 as an α-tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia and, when mutated, results in ADNSHL at the DFNA4 locus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • GPI-Linked Proteins / metabolism
  • Genes, Dominant*
  • Hearing Loss / genetics
  • Hearing Loss / metabolism*
  • Humans
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Myosin Heavy Chains / genetics*
  • Myosin Type II / genetics*
  • RNA, Messenger / genetics

Substances

  • CEACAM16 protein, mouse
  • Cell Adhesion Molecules
  • Extracellular Matrix Proteins
  • GPI-Linked Proteins
  • MYH14 protein, human
  • RNA, Messenger
  • TECTA protein, human
  • ceacam16 protein, human
  • Myosin Type II
  • Myosin Heavy Chains