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Inhibition of the serine protease HtrA1 by SerpinE2 suggests an extracellular proteolytic pathway in the control of neural crest migration.
- Source :
-
ELife [Elife] 2024 Apr 18; Vol. 12. Date of Electronic Publication: 2024 Apr 18. - Publication Year :
- 2024
-
Abstract
- We previously showed that SerpinE2 and the serine protease HtrA1 modulate fibroblast growth factor (FGF) signaling in germ layer specification and head-to-tail development of Xenopus embryos. Here, we present an extracellular proteolytic mechanism involving this serpin-protease system in the developing neural crest (NC). Knockdown of SerpinE2 by injected antisense morpholino oligonucleotides did not affect the specification of NC progenitors but instead inhibited the migration of NC cells, causing defects in dorsal fin, melanocyte, and craniofacial cartilage formation. Similarly, overexpression of the HtrA1 protease impaired NC cell migration and the formation of NC-derived structures. The phenotype of SerpinE2 knockdown was overcome by concomitant downregulation of HtrA1, indicating that SerpinE2 stimulates NC migration by inhibiting endogenous HtrA1 activity. SerpinE2 binds to HtrA1, and the HtrA1 protease triggers degradation of the cell surface proteoglycan Syndecan-4 (Sdc4). Microinjection of Sdc4 mRNA partially rescued NC migration defects induced by both HtrA1 upregulation and SerpinE2 downregulation. These epistatic experiments suggest a proteolytic pathway by a double inhibition mechanism.<br />SerpinE2 ┤HtrA1 protease ┤Syndecan-4 → NC cell migration.<br />Competing Interests: EP, JN, YP, LR, IM No competing interests declared<br /> (© 2023, Pera et al.)
- Subjects :
- Animals
Cell Movement genetics
Fibroblast Growth Factors metabolism
Signal Transduction
Xenopus laevis metabolism
Xenopus Proteins genetics
Xenopus Proteins metabolism
High-Temperature Requirement A Serine Peptidase 1 metabolism
Neural Crest embryology
Neural Crest metabolism
Serpin E2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 38634469
- Full Text :
- https://doi.org/10.7554/eLife.91864