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Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation

The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggest...

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Autores principales: Zallocchi, Marisa, Meehan, Daniel T., Delimont, Duane, Rutledge, Joseph, Gratton, Michael Anne, Flannery, John, Cosgrove, Dominic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281840/
https://www.ncbi.nlm.nih.gov/pubmed/22363448
http://dx.doi.org/10.1371/journal.pone.0030573
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author Zallocchi, Marisa
Meehan, Daniel T.
Delimont, Duane
Rutledge, Joseph
Gratton, Michael Anne
Flannery, John
Cosgrove, Dominic
author_facet Zallocchi, Marisa
Meehan, Daniel T.
Delimont, Duane
Rutledge, Joseph
Gratton, Michael Anne
Flannery, John
Cosgrove, Dominic
author_sort Zallocchi, Marisa
collection PubMed
description The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1−/− mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzer(av3J) mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well.
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spelling pubmed-32818402012-02-23 Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation Zallocchi, Marisa Meehan, Daniel T. Delimont, Duane Rutledge, Joseph Gratton, Michael Anne Flannery, John Cosgrove, Dominic PLoS One Research Article The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1−/− mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzer(av3J) mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well. Public Library of Science 2012-02-17 /pmc/articles/PMC3281840/ /pubmed/22363448 http://dx.doi.org/10.1371/journal.pone.0030573 Text en Zallocchi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zallocchi, Marisa
Meehan, Daniel T.
Delimont, Duane
Rutledge, Joseph
Gratton, Michael Anne
Flannery, John
Cosgrove, Dominic
Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation
title Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation
title_full Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation
title_fullStr Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation
title_full_unstemmed Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation
title_short Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation
title_sort role for a novel usher protein complex in hair cell synaptic maturation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281840/
https://www.ncbi.nlm.nih.gov/pubmed/22363448
http://dx.doi.org/10.1371/journal.pone.0030573
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