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

Jing Zheng, Katharine K. Miller, Tao Yang, Michael S. Hildebrand, A. Eliot Shearer, Adam P. DeLuca, Todd E. Scheetz, Jennifer Drummond, Steve E. Scherer, P. Kevin Legan, Richard J. Goodyear, Guy P. Richardson, Mary Ann Cheatham, Richard J. Smith, Peter Dallos

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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.

Original languageEnglish (US)
Pages (from-to)4218-4223
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number10
DOIs
StatePublished - Mar 8 2011

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Keywords

  • Cochlea
  • Deafness genes

ASJC Scopus subject areas

  • General

Cite this

Zheng, J., Miller, K. K., Yang, T., Hildebrand, M. S., Shearer, A. E., DeLuca, A. P., Scheetz, T. E., Drummond, J., Scherer, S. E., Legan, P. K., Goodyear, R. J., Richardson, G. P., Cheatham, M. A., Smith, R. J., & Dallos, P. (2011). Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with α-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). Proceedings of the National Academy of Sciences of the United States of America, 108(10), 4218-4223. https://doi.org/10.1073/pnas.1005842108