A Receptor-Like Inositol Lipid Phosphatase Is Required for the Maturation of Developing Cochlear Hair Bundles

Abstract

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.

Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5

“…24 Protein tyrosine phosphatase receptor Q (Ptprq), which is mislocalized as radixin in the jbg mice, and Myosin VI, key regulator of the proper localization of Ptprq, 25 might well participate in this complex too. Radixin, 26 Ptprq 25,27 Myosin VI 28 and Clic5-deficient mice 9 show loss of stereocilia at the bundle vertex and fusion of stereocilia in postnatal stage. This suggests that this multiprotein complex is essential for stable membrane-cytoskeletal attachments at the stereocilia base.…”

miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells

“…In diminuendo mice, the mutation affecting miR-96 leads to the down-regulation of Tmc1 (Fig. S5), which is a transmembrane protein required for the expression of adult-like biophysical characteristics in hair cells (8), and Ptprq (23), which is a component of the hair bundle stereocilia involved in their development (45). Furthermore, in the organ of Corti with mutant miR-96, Gfi1, which is a transcription factor critical for hair cell differentiation and survival from just before or at around birth (46), is down-regulated (23).…”

Familiar Meniere's disease restricted to 1.48 Mb on chromosome 12p12.3 by allelic and haplotype association

“…43,47 Mice mutant for several of the target genes for miRNAs exhibit deafness and hair cell degeneration, indicating the importance of this novel gene regulation in hearing loss. 48,49 To date, no intragenic miRNAs are annotated in the region associated with MD in our families. Further analysis is now required to clarify the molecular basis of the chromosome 12p12.3 region in MD, possibly with an emphasis on non-coding and non-genic sequences such as the two associated SNPs reported herein.…”