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FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes

FAM83H is essential for the formation of dental enamel because a mutation in the FAM83H gene causes amelogenesis imperfecta (AI). We previously reported that the overexpression of FAM83H often occurs and disorganizes the keratin cytoskeleton in colorectal cancer cells. We herein show that FAM83H reg...

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Autores principales: Kuga, Takahisa, Sasaki, Mitsuho, Mikami, Toshinari, Miake, Yasuo, Adachi, Jun, Shimizu, Maiko, Saito, Youhei, Koura, Minako, Takeda, Yasunori, Matsuda, Junichiro, Tomonaga, Takeshi, Nakayama, Yuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879633/
https://www.ncbi.nlm.nih.gov/pubmed/27222304
http://dx.doi.org/10.1038/srep26557
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author Kuga, Takahisa
Sasaki, Mitsuho
Mikami, Toshinari
Miake, Yasuo
Adachi, Jun
Shimizu, Maiko
Saito, Youhei
Koura, Minako
Takeda, Yasunori
Matsuda, Junichiro
Tomonaga, Takeshi
Nakayama, Yuji
author_facet Kuga, Takahisa
Sasaki, Mitsuho
Mikami, Toshinari
Miake, Yasuo
Adachi, Jun
Shimizu, Maiko
Saito, Youhei
Koura, Minako
Takeda, Yasunori
Matsuda, Junichiro
Tomonaga, Takeshi
Nakayama, Yuji
author_sort Kuga, Takahisa
collection PubMed
description FAM83H is essential for the formation of dental enamel because a mutation in the FAM83H gene causes amelogenesis imperfecta (AI). We previously reported that the overexpression of FAM83H often occurs and disorganizes the keratin cytoskeleton in colorectal cancer cells. We herein show that FAM83H regulates the organization of the keratin cytoskeleton and maintains the formation of desmosomes in ameloblastoma cells. FAM83H is expressed and localized on keratin filaments in human ameloblastoma cell lines and in mouse ameloblasts and epidermal germinative cells in vivo. FAM83H shows preferential localization to keratin filaments around the nucleus that often extend to cell-cell junctions. Alterations in the function of FAM83H by its overexpression, knockdown, or an AI-causing truncated mutant prevent the proper organization of the keratin cytoskeleton in ameloblastoma cells. Furthermore, the AI-causing mutant prevents desmosomal proteins from being localized to cell-cell junctions. The effects of the AI-causing mutant depend on its binding to and possible inhibition of casein kinase I (CK-1). The suppression of CK-1 by its inhibitor, D4476, disorganizes the keratin cytoskeleton. Our results suggest that AI caused by the FAM83H mutation is mediated by the disorganization of the keratin cytoskeleton and subsequent disruption of desmosomes in ameloblasts.
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spelling pubmed-48796332016-06-07 FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes Kuga, Takahisa Sasaki, Mitsuho Mikami, Toshinari Miake, Yasuo Adachi, Jun Shimizu, Maiko Saito, Youhei Koura, Minako Takeda, Yasunori Matsuda, Junichiro Tomonaga, Takeshi Nakayama, Yuji Sci Rep Article FAM83H is essential for the formation of dental enamel because a mutation in the FAM83H gene causes amelogenesis imperfecta (AI). We previously reported that the overexpression of FAM83H often occurs and disorganizes the keratin cytoskeleton in colorectal cancer cells. We herein show that FAM83H regulates the organization of the keratin cytoskeleton and maintains the formation of desmosomes in ameloblastoma cells. FAM83H is expressed and localized on keratin filaments in human ameloblastoma cell lines and in mouse ameloblasts and epidermal germinative cells in vivo. FAM83H shows preferential localization to keratin filaments around the nucleus that often extend to cell-cell junctions. Alterations in the function of FAM83H by its overexpression, knockdown, or an AI-causing truncated mutant prevent the proper organization of the keratin cytoskeleton in ameloblastoma cells. Furthermore, the AI-causing mutant prevents desmosomal proteins from being localized to cell-cell junctions. The effects of the AI-causing mutant depend on its binding to and possible inhibition of casein kinase I (CK-1). The suppression of CK-1 by its inhibitor, D4476, disorganizes the keratin cytoskeleton. Our results suggest that AI caused by the FAM83H mutation is mediated by the disorganization of the keratin cytoskeleton and subsequent disruption of desmosomes in ameloblasts. Nature Publishing Group 2016-05-25 /pmc/articles/PMC4879633/ /pubmed/27222304 http://dx.doi.org/10.1038/srep26557 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
Kuga, Takahisa
Sasaki, Mitsuho
Mikami, Toshinari
Miake, Yasuo
Adachi, Jun
Shimizu, Maiko
Saito, Youhei
Koura, Minako
Takeda, Yasunori
Matsuda, Junichiro
Tomonaga, Takeshi
Nakayama, Yuji
FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes
title FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes
title_full FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes
title_fullStr FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes
title_full_unstemmed FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes
title_short FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes
title_sort fam83h and casein kinase i regulate the organization of the keratin cytoskeleton and formation of desmosomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879633/
https://www.ncbi.nlm.nih.gov/pubmed/27222304
http://dx.doi.org/10.1038/srep26557
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