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Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear

Planar cell polarity (PCP) regulates coordinated cellular polarity among neighboring cells to establish a polarity axis parallel to the plane of the tissue. Disruption in PCP results in a range of developmental anomalies and diseases. A key feature of PCP is the polarized and asymmetric localization...

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Autores principales: Tower-Gilchrist, Cristy, Zlatic, Stephanie A., Yu, Dehong, Chang, Qing, Wu, Hao, Lin, Xi, Faundez, Victor, Chen, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741063/
https://www.ncbi.nlm.nih.gov/pubmed/31268833
http://dx.doi.org/10.1091/mbc.E16-08-0592
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author Tower-Gilchrist, Cristy
Zlatic, Stephanie A.
Yu, Dehong
Chang, Qing
Wu, Hao
Lin, Xi
Faundez, Victor
Chen, Ping
author_facet Tower-Gilchrist, Cristy
Zlatic, Stephanie A.
Yu, Dehong
Chang, Qing
Wu, Hao
Lin, Xi
Faundez, Victor
Chen, Ping
author_sort Tower-Gilchrist, Cristy
collection PubMed
description Planar cell polarity (PCP) regulates coordinated cellular polarity among neighboring cells to establish a polarity axis parallel to the plane of the tissue. Disruption in PCP results in a range of developmental anomalies and diseases. A key feature of PCP is the polarized and asymmetric localization of several membrane PCP proteins, which is essential to establish the polarity axis to orient cells coordinately. However, the machinery that regulates the asymmetric partition of PCP proteins remains largely unknown. In the present study, we show Van gogh-like 2 (Vangl2) in early and recycling endosomes as made evident by colocalization with diverse endosomal Rab proteins. Vangl2 biochemically interacts with adaptor protein-3 complex (AP-3). Using short hairpin RNA knockdown, we found that Vangl2 subcellular localization was modified in AP-3–depleted cells. Moreover, Vangl2 membrane localization within the cochlea is greatly reduced in AP-3–deficient mocha mice, which exhibit profound hearing loss. In inner ears from AP-3–deficient mocha mice, we observed PCP-dependent phenotypes, such as misorientation and deformation of hair cell stereociliary bundles and disorganization of hair cells characteristic of defects in convergent extension that is driven by PCP. These findings demonstrate a novel role of AP-3–mediated sorting mechanisms in regulating PCP proteins.
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spelling pubmed-67410632019-10-30 Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear Tower-Gilchrist, Cristy Zlatic, Stephanie A. Yu, Dehong Chang, Qing Wu, Hao Lin, Xi Faundez, Victor Chen, Ping Mol Biol Cell Articles Planar cell polarity (PCP) regulates coordinated cellular polarity among neighboring cells to establish a polarity axis parallel to the plane of the tissue. Disruption in PCP results in a range of developmental anomalies and diseases. A key feature of PCP is the polarized and asymmetric localization of several membrane PCP proteins, which is essential to establish the polarity axis to orient cells coordinately. However, the machinery that regulates the asymmetric partition of PCP proteins remains largely unknown. In the present study, we show Van gogh-like 2 (Vangl2) in early and recycling endosomes as made evident by colocalization with diverse endosomal Rab proteins. Vangl2 biochemically interacts with adaptor protein-3 complex (AP-3). Using short hairpin RNA knockdown, we found that Vangl2 subcellular localization was modified in AP-3–depleted cells. Moreover, Vangl2 membrane localization within the cochlea is greatly reduced in AP-3–deficient mocha mice, which exhibit profound hearing loss. In inner ears from AP-3–deficient mocha mice, we observed PCP-dependent phenotypes, such as misorientation and deformation of hair cell stereociliary bundles and disorganization of hair cells characteristic of defects in convergent extension that is driven by PCP. These findings demonstrate a novel role of AP-3–mediated sorting mechanisms in regulating PCP proteins. The American Society for Cell Biology 2019-08-15 /pmc/articles/PMC6741063/ /pubmed/31268833 http://dx.doi.org/10.1091/mbc.E16-08-0592 Text en © 2019 Tower-Gilchrist et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Tower-Gilchrist, Cristy
Zlatic, Stephanie A.
Yu, Dehong
Chang, Qing
Wu, Hao
Lin, Xi
Faundez, Victor
Chen, Ping
Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear
title Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear
title_full Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear
title_fullStr Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear
title_full_unstemmed Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear
title_short Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear
title_sort adaptor protein-3 complex is required for vangl2 trafficking and planar cell polarity of the inner ear
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741063/
https://www.ncbi.nlm.nih.gov/pubmed/31268833
http://dx.doi.org/10.1091/mbc.E16-08-0592
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