Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b


Autoři: Ding Ye aff001;  Xiaosi Wang aff001;  Changyong Wei aff001;  Mudan He aff001;  Houpeng Wang aff001;  Yanwu Wang aff001;  Zuoyan Zhu aff001;  Yonghua Sun aff001
Působiště autorů: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Innovative Academy for Seed Design, Chinese Academy of Sciences, Wuhan, China aff001;  College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China aff002;  School of Basic Medical Sciences, Wuhan University, Wuhan, China aff003
Vyšlo v časopise: Marcksb plays a key role in the secretory pathway of zebrafish Bmp2b. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008306
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008306

Souhrn

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.

Klíčová slova:

Embryos – Immunoblotting – Phosphorylation – Secretion – Secretory pathway – Zebrafish – BMP signaling – Guide RNA


Zdroje

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