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Beclin 1 regulates recycling endosome and is required for skin development in mice
Beclin 1 is a key regulator of autophagy and endocytosis. However, its autophagy-independent functions remain poorly understood. Here, we report that Beclin 1 regulates recycling endosome and is required for skin development in vivo. We first established keratinocyte-specific Beclin 1-knockout mice...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347619/ https://www.ncbi.nlm.nih.gov/pubmed/30701202 http://dx.doi.org/10.1038/s42003-018-0279-0 |
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author | Noguchi, Saori Honda, Shinya Saitoh, Tatsuya Matsumura, Hiroyuki Nishimura, Emi Akira, Shizuo Shimizu, Shigeomi |
author_facet | Noguchi, Saori Honda, Shinya Saitoh, Tatsuya Matsumura, Hiroyuki Nishimura, Emi Akira, Shizuo Shimizu, Shigeomi |
author_sort | Noguchi, Saori |
collection | PubMed |
description | Beclin 1 is a key regulator of autophagy and endocytosis. However, its autophagy-independent functions remain poorly understood. Here, we report that Beclin 1 regulates recycling endosome and is required for skin development in vivo. We first established keratinocyte-specific Beclin 1-knockout mice and found that these mutant mice died owing to severe impairment of epidermal barrier. Beclin 1 plays a role in autophagy and the endocytic pathway in cooperation with Atg14 and UVRAG, respectively, and keratinocyte-specific Atg14-knockout mice do not show any abnormal phenotypes, suggesting that Beclin 1 has a role in skin development via the endocytic pathway. Furthermore, we found that Beclin 1 deficiency causes mislocalization of integrins via a defect of recycling endosome, abnormal cell detachment of basal cells and their immature differentiation, and abnormal skin development. These results provide the first genetic evidence showing the roles of Beclin 1 in recycling endosome and skin development. |
format | Online Article Text |
id | pubmed-6347619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63476192019-01-30 Beclin 1 regulates recycling endosome and is required for skin development in mice Noguchi, Saori Honda, Shinya Saitoh, Tatsuya Matsumura, Hiroyuki Nishimura, Emi Akira, Shizuo Shimizu, Shigeomi Commun Biol Article Beclin 1 is a key regulator of autophagy and endocytosis. However, its autophagy-independent functions remain poorly understood. Here, we report that Beclin 1 regulates recycling endosome and is required for skin development in vivo. We first established keratinocyte-specific Beclin 1-knockout mice and found that these mutant mice died owing to severe impairment of epidermal barrier. Beclin 1 plays a role in autophagy and the endocytic pathway in cooperation with Atg14 and UVRAG, respectively, and keratinocyte-specific Atg14-knockout mice do not show any abnormal phenotypes, suggesting that Beclin 1 has a role in skin development via the endocytic pathway. Furthermore, we found that Beclin 1 deficiency causes mislocalization of integrins via a defect of recycling endosome, abnormal cell detachment of basal cells and their immature differentiation, and abnormal skin development. These results provide the first genetic evidence showing the roles of Beclin 1 in recycling endosome and skin development. Nature Publishing Group UK 2019-01-25 /pmc/articles/PMC6347619/ /pubmed/30701202 http://dx.doi.org/10.1038/s42003-018-0279-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Noguchi, Saori Honda, Shinya Saitoh, Tatsuya Matsumura, Hiroyuki Nishimura, Emi Akira, Shizuo Shimizu, Shigeomi Beclin 1 regulates recycling endosome and is required for skin development in mice |
title | Beclin 1 regulates recycling endosome and is required for skin development in mice |
title_full | Beclin 1 regulates recycling endosome and is required for skin development in mice |
title_fullStr | Beclin 1 regulates recycling endosome and is required for skin development in mice |
title_full_unstemmed | Beclin 1 regulates recycling endosome and is required for skin development in mice |
title_short | Beclin 1 regulates recycling endosome and is required for skin development in mice |
title_sort | beclin 1 regulates recycling endosome and is required for skin development in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347619/ https://www.ncbi.nlm.nih.gov/pubmed/30701202 http://dx.doi.org/10.1038/s42003-018-0279-0 |
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