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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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

Fingerprint

Tectorial Membrane
Outer Auditory Hair Cells
Carcinoembryonic Antigen
Cell Adhesion Molecules
Hearing Loss
Stereocilia
Proteins
Membrane Proteins
Cell Membrane
Messenger RNA
Mutation

Keywords

  • Cochlea
  • Deafness genes

ASJC Scopus subject areas

  • General

Cite this

Zheng, Jing ; Miller, Katharine K. ; Yang, Tao ; Hildebrand, Michael S. ; Shearer, A. Eliot ; DeLuca, Adam P. ; Scheetz, Todd E. ; Drummond, Jennifer ; Scherer, Steve E. ; Legan, P. Kevin ; Goodyear, Richard J. ; Richardson, Guy P. ; Cheatham, Mary Ann ; Smith, Richard J. ; Dallos, Peter. / Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with α-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 10. pp. 4218-4223.
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title = "Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with α-tectorin and is mutated in autosomal dominant hearing loss (DFNA4)",
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.",
keywords = "Cochlea, Deafness genes",
author = "Jing Zheng and Miller, {Katharine K.} and Tao Yang and Hildebrand, {Michael S.} and Shearer, {A. Eliot} and DeLuca, {Adam P.} and Scheetz, {Todd E.} and Jennifer Drummond and Scherer, {Steve E.} and Legan, {P. Kevin} and Goodyear, {Richard J.} and Richardson, {Guy P.} and Cheatham, {Mary Ann} and Smith, {Richard J.} and Peter Dallos",
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Zheng, J, Miller, KK, Yang, T, Hildebrand, MS, Shearer, AE, DeLuca, AP, Scheetz, TE, Drummond, J, Scherer, SE, Legan, PK, Goodyear, RJ, Richardson, GP, Cheatham, MA, Smith, RJ & 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, vol. 108, no. 10, pp. 4218-4223. https://doi.org/10.1073/pnas.1005842108

Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with α-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). / Zheng, Jing; Miller, Katharine K.; Yang, Tao; Hildebrand, Michael S.; Shearer, A. Eliot; DeLuca, Adam P.; Scheetz, Todd E.; Drummond, Jennifer; Scherer, Steve E.; Legan, P. Kevin; Goodyear, Richard J.; Richardson, Guy P.; Cheatham, Mary Ann; Smith, Richard J.; Dallos, Peter.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 10, 08.03.2011, p. 4218-4223.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with α-tectorin and is mutated in autosomal dominant hearing loss (DFNA4)

AU - Zheng, Jing

AU - Miller, Katharine K.

AU - Yang, Tao

AU - Hildebrand, Michael S.

AU - Shearer, A. Eliot

AU - DeLuca, Adam P.

AU - Scheetz, Todd E.

AU - Drummond, Jennifer

AU - Scherer, Steve E.

AU - Legan, P. Kevin

AU - Goodyear, Richard J.

AU - Richardson, Guy P.

AU - Cheatham, Mary Ann

AU - Smith, Richard J.

AU - Dallos, Peter

PY - 2011/3/8

Y1 - 2011/3/8

N2 - 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.

AB - 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.

KW - Cochlea

KW - Deafness genes

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U2 - 10.1073/pnas.1005842108

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JF - Proceedings of the National Academy of Sciences of the United States of America

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