PUBLICATION

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

Authors
Ye, D., Wang, X., Wei, C., He, M., Wang, H., Wang, Y., Zhu, Z., Sun, Y.
ID
ZDB-PUB-190924-12
Date
2019
Source
PLoS Genetics   15: e1008306 (Journal)
Registered Authors
He, Mudan, Sun, Yonghua, Wei, Changyong, Ye, Ding, Zhu, Zuoyan
Keywords
none
MeSH Terms
  • Animals
  • Body Patterning/physiology
  • Bone Morphogenetic Protein 2/metabolism*
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/genetics
  • Embryonic Development/physiology
  • Female
  • HSP70 Heat-Shock Proteins/metabolism
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Secretory Pathway
  • Signal Transduction
  • Transforming Growth Factor beta/metabolism
  • Zebrafish/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
PubMed
31545789 Full text @ PLoS Genet.
Abstract
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.
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Fish
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Errata and Notes