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Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells.

Usher syndrome type IIA (USH2A), characterized by progressive photoreceptor degeneration and congenital moderate hearing loss, is the most common subtype of Usher syndrome. In this article, we show that the USH2A protein, also known as usherin, is an exceptionally large ( approximately 600-kDa) matrix protein expressed specifically in retinal photoreceptors and developing cochlear hair cells. In mammalian photoreceptors, usherin is localized to a spatially restricted membrane microdomain at the apical inner segment recess that wraps around the connecting cilia, corresponding to the periciliary ridge complex described for amphibian photoreceptors. In sensory hair cells of the cochlea, it is associated transiently with the hair bundles during postnatal development. Targeted disruption of the Ush2a gene in mice leads to progressive photoreceptor degeneration and a moderate but nonprogressive hearing impairment, mimicking the visual and hearing deficits in USH2A patients. These data suggest that usherin is required for the long-term maintenance of retinal photoreceptors and for the development of cochlear hair cells. We propose a model in which usherin in photoreceptors is tethered via its C terminus to the plasma membrane and its large extracellular domain projecting into the periciliary matrix, where they may interact with the connecting cilium to fulfill important structural or signaling roles.

Pubmed ID: 17360538

Authors

  • Liu X
  • Bulgakov OV
  • Darrow KN
  • Pawlyk B
  • Adamian M
  • Liberman MC
  • Li T

Journal

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

Publication Data

March 13, 2007

Associated Grants

  • Agency: NIDCD NIH HHS, Id: P30 DC 05209
  • Agency: NIDCD NIH HHS, Id: P30 DC005209
  • Agency: NEI NIH HHS, Id: P30 EY 14104
  • Agency: NIDCD NIH HHS, Id: R01 DC 00188
  • Agency: NIDCD NIH HHS, Id: R01 DC000188
  • Agency: NIDCD NIH HHS, Id: R01 DC000188-27
  • Agency: NEI NIH HHS, Id: R01 EY 10309

Mesh Terms

  • Animals
  • Cochlea
  • Extracellular Matrix Proteins
  • Gene Expression Regulation, Developmental
  • Hair Cells, Auditory
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Retina
  • Retinitis Pigmentosa