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Zhou Q, Lei L, Zhang H, et al. Proprotein convertase furina is required for heart development in zebrafish. J Cell Sci. 2021;134(21)doi: 10.1242/jcs.258432.
Zhou, Q., Lei, L., Zhang, H., Chiu, S. C., Gao, L., Yang, R., Wei, W., Peng, G., Zhu, X., & Xiong, J. W. (2021). Proprotein convertase furina is required for heart development in zebrafish. Journal of cell science, 134(21), . https://doi.org/10.1242/jcs.258432
Zhou, Qinchao, et al. "Proprotein convertase furina is required for heart development in zebrafish." Journal of cell science vol. 134,21 (2021). doi: https://doi.org/10.1242/jcs.258432
Zhou Q, Lei L, Zhang H, Chiu SC, Gao L, Yang R, Wei W, Peng G, Zhu X, Xiong JW. Proprotein convertase furina is required for heart development in zebrafish. J Cell Sci. 2021 Nov 01;134(21). doi: 10.1242/jcs.258432. Epub 2021 Nov 05. PMID: 34622921.
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J Cell Sci. 2021 Nov 01;134(21). doi: 10.1242/jcs.258432. Epub 2021 Nov 05.

Proprotein convertase furina is required for heart development in zebrafish.

Journal of cell science

Qinchao Zhou, Lei Lei, Hefei Zhang, Shih-Ching Chiu, Lu Gao, Ran Yang, Wensheng Wei, Gang Peng, Xiaojun Zhu, Jing-Wei Xiong

Affiliations

  1. Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100871, China.
  2. Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
  3. School of Life Sciences, Peking University, Beijing 100871, China.

PMID: 34622921 DOI: 10.1242/jcs.258432

Abstract

Cardiac looping and trabeculation are key processes during cardiac chamber maturation. However, the underlying mechanisms remain incompletely understood. Here, we report the isolation, cloning and characterization of the proprotein convertase furina from the cardiovascular mutant loft in zebrafish. loft is an ethylnitrosourea-induced mutant and has evident defects in the cardiac outflow tract, heart looping and trabeculation, the craniofacial region and pharyngeal arch arteries. Positional cloning revealed that furina mRNA was barely detectable in loft mutants, and loft failed to complement the TALEN-induced furina mutant pku338, confirming that furina is responsible for the loft mutant phenotypes. Mechanistic studies demonstrated that Notch reporter Tg(tp1:mCherry) signals were largely eliminated in mutant hearts, and overexpression of the Notch intracellular domain partially rescued the mutant phenotypes, probably due to the lack of Furina-mediated cleavage processing of Notch1b proteins, the only Notch receptor expressed in the heart. Together, our data suggest a potential post-translational modification of Notch1b proteins via the proprotein convertase Furina in the heart, and unveil the function of the Furina-Notch1b axis in cardiac looping and trabeculation in zebrafish, and possibly in other organisms.

© 2021. Published by The Company of Biologists Ltd.

Keywords: Furina ; Loft mutant; Cardiac trabeculation; Heart looping; Zebrafish

Conflict of interest statement

Competing interests The authors declare no competing or financial interests.

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