ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Splice-site A choice targets plasma-membrane Ca2+-ATPase isoform 2 to hair bundles.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
- CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Inhibition of a transcriptional repressor rescues hearing in a splicing factor-deficient mouse.Life science alliance · 2020Article
- Tonotopy in calcium homeostasis and vulnerability of cochlear hair cells.Hearing research · 2019Review
- De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment.Human genetics · 2019Article
- Differential expression of PMCA2 mRNA isoforms in a cohort of Spanish patients with breast tumor types.Oncology letters · 2018Article
- Evidence for a role of plasma membrane calcium pumps in neurodegenerative disease: Recent developments.Neuroscience letters · 2018Review
- Metabolic regulation of the PMCA: Role in cell death and survival.Cell calcium · 2018Review
- Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells.Frontiers in cellular neuroscience · 2018Article
- Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs.Development (Cambridge, England) · 2016Article
- Article
- Ionic leakage underlies a gain-of-function effect of dominant disease mutations affecting diverse P-type ATPases.Nature genetics · 2014Article
- The candidate splicing factor Sfswap regulates growth and patterning of inner ear sensory organs.PLoS genetics · 2014Article
- Electrical tuning and transduction in short hair cells of the chicken auditory papilla.Journal of neurophysiology · 2013Article
- Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48.Nature genetics · 2012Article
- The development, distribution and density of the plasma membrane calcium ATPase 2 calcium pump in rat cochlear hair cells.The European journal of neuroscience · 2012Article
- Calcium signaling in the cochlea - Molecular mechanisms and physiopathological implications.Cell communication and signaling : CCS · 2012Article
- Plasma membrane calcium pump (PMCA) isoform 4 is targeted to the apical membrane by the w-splice insert from PMCA2.Cell calcium · 2012Article
- Improved biolistic transfection of hair cells.PloS one · 2012Article
- Apical localization of PMCA2w/b is enhanced in terminally polarized MDCK cells.Biochemical and biophysical research communications · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Localization of mechanotransduction in sensory hair cells to hair bundles requires selective targeting of essential proteins to specific locations. Isoform 2 of the plasma-membrane Ca2+-ATPase (PMCA2), required for hearing and balance, is found exclusively in hair bundles. We determined the contribution of splicing at the two major splicing sites (A and C) to hair-cell targeting of PMCA2. When PMCA2 isoforms were immunoprecipitated from purified hair bundles of rat utricle, 2w was the only site A variant detected; moreover, immunocytochemistry for 2w in rat vestibular and cochlear tissues indicated that this splice form was located solely in bundles. To demonstrate the necessity of the 2w sequence, we transfected hair cells with PMCA2 containing different variants at splice sites A and C. Although native hair bundles exclusively use the 2a form at splice-site C, epitope-tagged PMCA2w/a and PMCA2w/b were both concentrated in bundles, indicating that site C is not involved in bundle targeting. In contrast, PMCA2z/a was excluded from bundles and was instead targeted to the basolateral plasma membrane. Bundle-specific targeting of PMCA2w/a tagged with green fluorescent protein (GFP) was diminished, suggesting that GFP interfered with splice-site A. Together, these data demonstrate that PMCA2w/a is the hair-bundle isoform of PMCA in rat hair cells and that 2w targets PMCA2 to bundles. The 2w sequence is thus the first targeting signal identified for a hair-bundle membrane protein; moreover, the striking distribution of inner-ear PMCA isoforms dictated by selective targeting suggests a critical functional role for segregated pathways of Ca2+ transport.
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Registered trials
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