A receptor-like inositol lipid phosphatase is required for the maturation of developing cochlear hair bundles
| Autor: | Anush Oganesian, Dan F. Bowen-Pope, M. B. Wright, Guy P. Richardson, Walter Marcotti, Ronald A. Seifert, Scott A. Coats, Richard J. Goodyear, Corné J. Kros, C. J. Booth, P. K. Legan |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Genetically modified mouse
Patch-Clamp Techniques Cell Survival Phalloidine Stereocilia (inner ear) Phosphatase Molecular Sequence Data Mice Transgenic Protein tyrosine phosphatase Cell Separation Biology Deafness Phosphatidylinositols Mechanotransduction Cellular 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Hair Cells Auditory medicine otorhinolaryngologic diseases Animals Inner ear Inositol Cilia RNA Messenger Receptor 030304 developmental biology Mice Knockout 0303 health sciences integumentary system General Neuroscience Receptor-Like Protein Tyrosine Phosphatases Class 3 Gene Expression Regulation Developmental Phosphoric Monoester Hydrolases Cell biology Cochlea medicine.anatomical_structure Biochemistry chemistry Antigens Surface Hair cell sense organs Protein Tyrosine Phosphatases Chickens 030217 neurology & neurosurgery Cellular/Molecular |
| ISSN: | 0270-6474 |
| Popis: | A screen for protein tyrosine phosphatases (PTPs) expressed in the chick inner ear yielded a high proportion of clones encoding an avian ortholog of protein tyrosine phosphatase receptor Q (Ptprq), a receptor-like PTP. Ptprq was first identified as a transcript upregulated in rat kidney in response to glomerular nephritis and has recently been shown to be active against inositol phospholipids. An antibody to the intracellular domain of Ptprq, anti-Ptprq, stains hair bundles in mice and chicks. In the chick ear, the distribution of Ptprq is almost identical to that of the 275 kDa hair-cell antigen (HCA), a component of hair-bundle shaft connectors recognized by a monoclonal antibody (mAb) that stains inner-ear hair bundles and kidney glomeruli. Furthermore, anti-Ptprq immunoblots a 275 kDa polypeptide immunoprecipitated by the anti-HCA mAb from the avian inner ear, indicating that the HCA and Ptprq are likely to be the same molecule. In two transgenic mouse strains with different mutations in Ptprq, anti-Ptprq immunoreactivity cannot be detected in the ear. Shaft connectors are absent from mutant vestibular hair bundles, but the stereocilia forming the hair bundle are not splayed, indicating that shaft connectors are not necessary to hold the stereocilia together; however, the mice show rapid postnatal deterioration in cochlear hair-bundle structure, associated with smaller than normal transducer currents with otherwise normal adaptation properties, a progressive loss of basal-coil cochlear hair cells, and deafness. These results reveal that Ptprq is required for formation of the shaft connectors of the hair bundle, the normal maturation of cochlear hair bundles, and the long-term survival of high-frequency auditory hair cells. |
| Databáze: | OpenAIRE |
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