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Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function
Cadherin-related 23 (CDH23) is an adhesive protein important for hearing and vision, while CAMSAP3/Marshalin is a microtubule (MT) minus-end binding protein that regulates MT networks. Although both CDH23 and CAMSAP3/Marshalin are expressed in the organ of Corti, and carry several protein-protein in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923861/ https://www.ncbi.nlm.nih.gov/pubmed/27349180 http://dx.doi.org/10.1038/srep28706 |
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author | Takahashi, Satoe Mui, Vincent J. Rosenberg, Samuel K. Homma, Kazuaki Cheatham, Mary Ann Zheng, Jing |
author_facet | Takahashi, Satoe Mui, Vincent J. Rosenberg, Samuel K. Homma, Kazuaki Cheatham, Mary Ann Zheng, Jing |
author_sort | Takahashi, Satoe |
collection | PubMed |
description | Cadherin-related 23 (CDH23) is an adhesive protein important for hearing and vision, while CAMSAP3/Marshalin is a microtubule (MT) minus-end binding protein that regulates MT networks. Although both CDH23 and CAMSAP3/Marshalin are expressed in the organ of Corti, and carry several protein-protein interaction domains, no functional connection between these two proteins has been proposed. In this report, we demonstrate that the C isoform of CDH23 (CDH23-C) directly binds to CAMSAP3/Marshalin and modifies its function by inhibiting CAMSAP3/Marshalin-induced bundle formation, a process that requires a tubulin-binding domain called CKK. We further identified a conserved N-terminal region of CDH23-C that binds to the CKK domain. This CKK binding motif (CBM) is adjacent to the domain that interacts with harmonin, a binding partner of CDH23 implicated in deafness. Because the human Usher Syndrome 1D-associated mutation, CDH23 R3175H, maps to the CBM, we created a matched mutation in mouse CDH23-C at R55H. Both in vivo and in vitro assays decreased the ability of CDH23-C to interact with CAMSAP3/Marshalin, indicating that the interaction between CDH23 and CAMSAP3/Marshalin plays a vital role in hearing and vision. Together, our data suggest that CDH23-C is a CAMSAP3/Marshalin-binding protein that can modify MT networks indirectly through its interaction with CAMSAP3/Marshalin. |
format | Online Article Text |
id | pubmed-4923861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49238612016-06-28 Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function Takahashi, Satoe Mui, Vincent J. Rosenberg, Samuel K. Homma, Kazuaki Cheatham, Mary Ann Zheng, Jing Sci Rep Article Cadherin-related 23 (CDH23) is an adhesive protein important for hearing and vision, while CAMSAP3/Marshalin is a microtubule (MT) minus-end binding protein that regulates MT networks. Although both CDH23 and CAMSAP3/Marshalin are expressed in the organ of Corti, and carry several protein-protein interaction domains, no functional connection between these two proteins has been proposed. In this report, we demonstrate that the C isoform of CDH23 (CDH23-C) directly binds to CAMSAP3/Marshalin and modifies its function by inhibiting CAMSAP3/Marshalin-induced bundle formation, a process that requires a tubulin-binding domain called CKK. We further identified a conserved N-terminal region of CDH23-C that binds to the CKK domain. This CKK binding motif (CBM) is adjacent to the domain that interacts with harmonin, a binding partner of CDH23 implicated in deafness. Because the human Usher Syndrome 1D-associated mutation, CDH23 R3175H, maps to the CBM, we created a matched mutation in mouse CDH23-C at R55H. Both in vivo and in vitro assays decreased the ability of CDH23-C to interact with CAMSAP3/Marshalin, indicating that the interaction between CDH23 and CAMSAP3/Marshalin plays a vital role in hearing and vision. Together, our data suggest that CDH23-C is a CAMSAP3/Marshalin-binding protein that can modify MT networks indirectly through its interaction with CAMSAP3/Marshalin. Nature Publishing Group 2016-06-28 /pmc/articles/PMC4923861/ /pubmed/27349180 http://dx.doi.org/10.1038/srep28706 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Takahashi, Satoe Mui, Vincent J. Rosenberg, Samuel K. Homma, Kazuaki Cheatham, Mary Ann Zheng, Jing Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function |
title | Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function |
title_full | Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function |
title_fullStr | Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function |
title_full_unstemmed | Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function |
title_short | Cadherin 23-C Regulates Microtubule Networks by Modifying CAMSAP3’s Function |
title_sort | cadherin 23-c regulates microtubule networks by modifying camsap3’s function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923861/ https://www.ncbi.nlm.nih.gov/pubmed/27349180 http://dx.doi.org/10.1038/srep28706 |
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