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Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b
During vertebrate early embryogenesis, the ventral development is directed by the ventral-to-dorsal activity gradient of the bone morphogenetic protein (BMP) signaling. As secreted ligands, the extracellular traffic of BMP has been extensively studied. However, it remains poorly understood that how...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776368/ https://www.ncbi.nlm.nih.gov/pubmed/31545789 http://dx.doi.org/10.1371/journal.pgen.1008306 |
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author | Ye, Ding Wang, Xiaosi Wei, Changyong He, Mudan Wang, Houpeng Wang, Yanwu Zhu, Zuoyan Sun, Yonghua |
author_facet | Ye, Ding Wang, Xiaosi Wei, Changyong He, Mudan Wang, Houpeng Wang, Yanwu Zhu, Zuoyan Sun, Yonghua |
author_sort | Ye, Ding |
collection | PubMed |
description | During vertebrate early embryogenesis, the ventral development is directed by the ventral-to-dorsal activity gradient of the bone morphogenetic protein (BMP) signaling. As secreted ligands, the extracellular traffic of BMP has been extensively studied. However, it remains poorly understood that how BMP ligands are secreted from BMP-producing cells. In this work, we show the dominant role of Marcksb controlling the secretory process of Bmp2b via interaction with Hsp70 in vivo. We firstly carefully characterized the role of Marcksb in promoting BMP signaling during dorsoventral axis formation through knockdown approach. We then showed that Marcksb cell autonomously regulates the trafficking of Bmp2b from producing cell to the extracellular space and both the total and the extracellular Bmp2b was decreased in Marcksb-deficient embryos. However, neither the zygotic mutant of marcksb (Zmarcksb) nor the maternal zygotic mutant of marcksb (MZmarcksb) showed any defects of dorsalization. In contrast, the MZmarcksb embryos even showed increased BMP signaling activity as measured by expression of BMP targets, phosphorylated Smad1/5/9 levels and imaging of Bmp2b, suggesting that a phenomenon of “genetic over-compensation” arose. Finally, we revealed that the over-compensation effects of BMP signaling in MZmarcksb was achieved through a sequential up-regulation of MARCKS-family members Marcksa, Marcksl1a and Marcksl1b, and MARCKS-interacting protein Hsp70.3. We concluded that the Marcksb modulates BMP signaling through regulating the secretory pathway of Bmp2b. |
format | Online Article Text |
id | pubmed-6776368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-67763682019-10-11 Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b Ye, Ding Wang, Xiaosi Wei, Changyong He, Mudan Wang, Houpeng Wang, Yanwu Zhu, Zuoyan Sun, Yonghua PLoS Genet Research Article During vertebrate early embryogenesis, the ventral development is directed by the ventral-to-dorsal activity gradient of the bone morphogenetic protein (BMP) signaling. As secreted ligands, the extracellular traffic of BMP has been extensively studied. However, it remains poorly understood that how BMP ligands are secreted from BMP-producing cells. In this work, we show the dominant role of Marcksb controlling the secretory process of Bmp2b via interaction with Hsp70 in vivo. We firstly carefully characterized the role of Marcksb in promoting BMP signaling during dorsoventral axis formation through knockdown approach. We then showed that Marcksb cell autonomously regulates the trafficking of Bmp2b from producing cell to the extracellular space and both the total and the extracellular Bmp2b was decreased in Marcksb-deficient embryos. However, neither the zygotic mutant of marcksb (Zmarcksb) nor the maternal zygotic mutant of marcksb (MZmarcksb) showed any defects of dorsalization. In contrast, the MZmarcksb embryos even showed increased BMP signaling activity as measured by expression of BMP targets, phosphorylated Smad1/5/9 levels and imaging of Bmp2b, suggesting that a phenomenon of “genetic over-compensation” arose. Finally, we revealed that the over-compensation effects of BMP signaling in MZmarcksb was achieved through a sequential up-regulation of MARCKS-family members Marcksa, Marcksl1a and Marcksl1b, and MARCKS-interacting protein Hsp70.3. We concluded that the Marcksb modulates BMP signaling through regulating the secretory pathway of Bmp2b. Public Library of Science 2019-09-23 /pmc/articles/PMC6776368/ /pubmed/31545789 http://dx.doi.org/10.1371/journal.pgen.1008306 Text en © 2019 Ye 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ye, Ding Wang, Xiaosi Wei, Changyong He, Mudan Wang, Houpeng Wang, Yanwu Zhu, Zuoyan Sun, Yonghua Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b |
title | Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b |
title_full | Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b |
title_fullStr | Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b |
title_full_unstemmed | Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b |
title_short | Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b |
title_sort | marcksb plays a key role in the secretory pathway of zebrafish bmp2b |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776368/ https://www.ncbi.nlm.nih.gov/pubmed/31545789 http://dx.doi.org/10.1371/journal.pgen.1008306 |
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