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The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions

Item Type:Article
Title:The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions
Creators Name:Siemens, J. and Kazmierczak, P. and Reynolds, A. and Sticker, M. and Littlewood-Evans, A. and Mueller, U.
Abstract:Usher syndrome type 1 (USH1) patients suffer from sensorineuronal deafness, vestibular dysfunction, and visual impairment. Several genetic loci have been linked to USH1, and four of the relevant genes have been identified. They encode the unconventional myosin VIIa, the PDZ-domain protein harmonin, and the putative adhesion receptors cadherin 23 (CDH23) and protocadherin 15 (PCDH15). We show here that CDH23 and harmonin form a protein complex. Two PDZ domains in harmonin interact with two complementary binding surfaces in the CDH23 cytoplasmic domain. One of the binding surfaces is disrupted by sequences encoded by an alternatively spliced CDH23 exon that is expressed in the ear, but not the retina. In the ear, CDH23 and harmonin are expressed in the stereocilia of hair cells, and in the retina within the photoreceptor cell layer. Because CDH23-deficient mice have splayed stereocilia, our data suggest that CDH23 and harmonin are part of a transmembrane complex that connects stereocilia into a bundle. Defects in the formation of this complex are predicted to disrupt stereocilia bundles and cause deafness in USH1 patients.
Keywords:Amino Acid Sequence, Binding Sites, Cadherins, Carrier Proteins, Sensorineural Hearing Loss, Immune Sera, Immunohistochemistry, Molecular Sequence Data, Protein Binding, Retinitis Pigmentosa, Syndrome, Animals, Mice, Rabbits
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:99
Number:23
Page Range:14946-14951
Date:12 November 2002
Official Publication:https://doi.org/10.1073/pnas.232579599
PubMed:View item in PubMed

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