ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing.Nature communications · 2025Article
- Functional Studies of Deafness-Associated Pendrin and Prestin Variants.International journal of molecular sciences · 2024Article
- The morphological and functional diversity of apical microvilli.Journal of anatomy · 2023Review
- ARNSHL gene identification: past, present and future.Molecular genetics and genomics : MGG · 2022Review
- Identification of IQGAP1 as a SLC26A4 (Pendrin)-Binding Protein in the Kidney.Frontiers in molecular biosciences · 2022Article
- Usher Syndrome: Genetics of a Human Ciliopathy.International journal of molecular sciences · 2021Review
- Propagation of F-actin disassembly via Myosin15-Mical interactions.Science advances · 2021Article
- Inframe deletion of humanJournal of medical genetics · 2018Article
- Article
- Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.Nature biotechnology · 2017Article
- The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells.Human molecular genetics · 2017Article
- Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3's Function.Scientific reports · 2016Article
- Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities.Biochimica et biophysica acta · 2015Review
- A short splice form of Xin-actin binding repeat containing 2 (XIRP2) lacking the Xin repeats is required for maintenance of stereocilia morphology and hearing function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Tyrosine motifs are required for prestin basolateral membrane targeting.Biology open · 2015Article
- Characterization and regulation of an additional actin-filament-binding site in large isoforms of the stereocilia actin-bundling protein espin.Journal of cell science · 2014Article
- Article
- CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI.Cytoskeleton (Hoboken, N.J.) · 2014Article
- Cyclic nucleotide-gated channel α-3 (CNGA3) interacts with stereocilia tip-link cadherin 23 + exon 68 or alternatively with myosin VIIa, two proteins required for hair cell mechanotransduction.The Journal of biological chemistry · 2013Article
- Beyond generalized hair cells: molecular cues for hair cell types.Hearing research · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
We have developed an advantageous epithelial cell transfection model for examining the targeting, interactions, and mutations of hair cell proteins. When expressed in LLC-PK1-CL4 epithelial cells (CL4 cells), the outer hair cell protein prestin showed faithful domain-specific targeting to the basolateral plasma membrane. We examined the consequences of mutations affecting prestin activity and assigned a targeting role to the cytoplasmic tail. The stereociliary link protein cadherin 23 (Cdh23) was targeted to the plasma membrane of CL4 cell microvilli, the topological equivalent of stereocilia. In cells coexpressing the Cdh23 cytoplasmic binding protein harmonin, a large fraction of harmonin became colocalized with Cdh23 in microvilli. Using this assay and in vitro protein binding assays, we formulated an alternative model for Cdh23-harmonin binding, in which the primary interaction is between the harmonin N-domain and a 35-residue internal peptide in the Cdh23 cytoplasmic tail. Contrary to a previous model, we found no role for the Cdh23 C-terminal PDZ (PSD-95/Dlg/ZO-1)-binding motif and observed that Cdh23 bound similar levels of harmonin with or without the exon 68 peptide. We also examined two proteins involved in stereocilium elongation. The stereociliary actin-bundling protein espin was targeted to CL4 cell microvilli and caused microvillar elongation, whereas espin with the c.2469delGTCA or c.1988delAGAG human deafness mutation showed defects in microvillar targeting and elongation. The unconventional myosin motor myosin XVa accumulated at the tips of espin-elongated microvilli, by analogy to its location in stereocilia, whereas myosin XVa with the c.4351G>A or c.4669A>G human deafness mutation did not, revealing functional deficits in motor activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.