Hair-Bundle Links: Genetics as the Gateway to Function
Up to five distinct cell-surface specializations interconnect the stereocilia and the kinocilium of the mature hair bundle in some species: kinocilial links, tip links, top connectors, shaft connectors, and ankle links. In developing hair bundles, transient lateral links are prominent. Mutations in...
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| Published in: | Cold Spring Harbor perspectives in medicine Vol. 9; no. 12; p. a033142 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
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United States
Cold Spring Harbor Laboratory Press
01-12-2019
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| Abstract | Up to five distinct cell-surface specializations interconnect the stereocilia and the kinocilium of the mature hair bundle in some species: kinocilial links, tip links, top connectors, shaft connectors, and ankle links. In developing hair bundles, transient lateral links are prominent. Mutations in genes encoding proteins associated with these links cause Usher deafness/blindness syndrome or nonsyndromic (isolated) forms of human hereditary deafness, and mice with constitutive or conditional alleles of these genes have provided considerable insight into the molecular composition and function of the different links. We describe the structure of these links and review evidence showing CDH23 and PCDH15 are components of the tip, kinocilial, and transient-lateral links, that stereocilin (STRC) and protein tyrosine phosphatase (PTPRQ) are associated with top and shaft connectors, respectively, and that USH2A and ADGRV1 are associated with the ankle links. Whereas tip links are required for mechanoelectrical transduction, all link proteins play key roles in the normal development and/or the maintenance of hair bundle structure and function. Recent crystallographic and single-particle analyses of PCDH15 and CDH23 provide insight as to how the structure of tip link may contribute to the elastic element predicted to lie in series with the hair cell's mechanoelectrical transducer channel. |
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| AbstractList | Up to five distinct cell-surface specializations interconnect the stereocilia and the kinocilium of the mature hair bundle in some species: kinocilial links, tip links, top connectors, shaft connectors, and ankle links. In developing hair bundles, transient lateral links are prominent. Mutations in genes encoding proteins associated with these links cause Usher deafness/blindness syndrome or nonsyndromic (isolated) forms of human hereditary deafness, and mice with constitutive or conditional alleles of these genes have provided considerable insight into the molecular composition and function of the different links. We describe the structure of these links and review evidence showing CDH23 and PCDH15 are components of the tip, kinocilial, and transient-lateral links, that stereocilin (STRC) and protein tyrosine phosphatase (PTPRQ) are associated with top and shaft connectors, respectively, and that USH2A and ADGRV1 are associated with the ankle links. Whereas tip links are required for mechanoelectrical transduction, all link proteins play key roles in the normal development and/or the maintenance of hair bundle structure and function. Recent crystallographic and single-particle analyses of PCDH15 and CDH23 provide insight as to how the structure of tip link may contribute to the elastic element predicted to lie in series with the hair cell's mechanoelectrical transducer channel. |
| Author | Richardson, Guy P Petit, Christine |
| AuthorAffiliation | 1 Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom 2 Institut Pasteur, 75724 Paris Cedex 15, France 3 Collège de France, 75231 Paris Cedex 05, France |
| AuthorAffiliation_xml | – name: 1 Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom – name: 2 Institut Pasteur, 75724 Paris Cedex 15, France – name: 3 Collège de France, 75231 Paris Cedex 05, France |
| Author_xml | – sequence: 1 givenname: Guy P surname: Richardson fullname: Richardson, Guy P organization: Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom – sequence: 2 givenname: Christine surname: Petit fullname: Petit, Christine organization: Collège de France, 75231 Paris Cedex 05, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30617060$$D View this record in MEDLINE/PubMed |
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| Title | Hair-Bundle Links: Genetics as the Gateway to Function |
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