ZFIN ID: ZDB-PUB-190227-6
Myosin Vb is required for correct trafficking of N-cadherin and cardiac chamber ballooning
Grassini, D.R., Da Silva, J., Hall, T.E., Baillie, G.J., Simons, C., Parton, R.G., Hogan, B.M., Smith, K.A.
Date: 2019
Source: Developmental dynamics : an official publication of the American Association of Anatomists   248(4): 284-295 (Journal)
Registered Authors: Da Silva, Jason, Grassini, Daniela, Hall, Thomas, Hogan, Ben M., Parton, Robert G., Smith, Kelly
Keywords: Heart morphogenesis, N-cadherin, chamber ballooning, myo5b
MeSH Terms:
  • Animals
  • Cadherins/metabolism*
  • Cell Shape
  • Cytoskeleton/metabolism
  • Cytoskeleton/ultrastructure*
  • Endosomes/metabolism
  • Heart/growth & development*
  • Humans
  • Myocardium/cytology
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Myocytes, Cardiac/ultrastructure
  • Myosin Type V/genetics
  • Myosin Type V/physiology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
PubMed: 30801852 Full text @ Dev. Dyn.
During heart morphogenesis, the cardiac chambers undergo ballooning: a process involving regionalized elongation of cardiomyocytes. Cardiomyocyte shape changes require reorganisation of the actin cytoskeleton however the genetic regulation of this process is not well understood.
From a forward genetic screen, we identified the zebrafish uq23ks mutant which manifests chamber ballooning defects. Whole-genome sequencing-mapping identified a truncating mutation in the gene, myo5b. myo5b encodes an atypical myosin required for endosome recycling and, consistent with this, increased vesicles were observed in myo5b mutant cardiomyocytes. Expression of RFP-Rab11a (a recycling endosome marker) confirmed increased recycling endosomes in cardiomyocytes of myo5b mutants. To investigate potential cargo of MyoVb-associated vesicles, we examined the Adherens Junction protein, N-cadherin. N-cadherin appeared mispatterned at cell junctions and an increase in the number of intracellular particles was also apparent. Co-localisation with RFP-Rab11a confirmed increased N-cadherin-positive recycling endosomes, demonstrating N-cadherin trafficking is perturbed in myo5b mutants. Finally, Phalloidin staining showed disorganised F-actin in myo5b cardiomyocytes, suggesting the cytoskeleton fails to remodel, obstructing chamber ballooning.
MyoVb is required for cardiomyocyte endosomal recycling and appropriate N-cadherin localisation during the onset of chamber ballooning. Cardiomyocytes lacking MyoVb are unable to reorganize their actin cytoskeleton, resulting in failed chamber ballooning. This article is protected by copyright. All rights reserved.