Back to Search
Start Over
Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 Mar 13; Vol. 104 (11), pp. 4413-8. Date of Electronic Publication: 2007 Mar 05. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Confocal
Molecular Sequence Data
Retinitis Pigmentosa metabolism
Cochlea growth & development
Extracellular Matrix Proteins physiology
Gene Expression Regulation, Developmental
Hair Cells, Auditory growth & development
Retina growth & development
Retinitis Pigmentosa pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 104
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 17360538
- Full Text :
- https://doi.org/10.1073/pnas.0610950104