Key result
MyoVb mutation disrupts cardiomyocyte endosomal recycling and N-cadherin localization, preventing actin cytoskeleton reorganization and resulting in failed cardiac chamber ballooning.
Why the study?
Cardiomyocyte shape changes during cardiac chamber ballooning require reorganization of the actin cytoskeleton, but the genetic regulation of this process is not well understood.
MyoVb is essential for cardiomyocyte endosomal recycling, appropriate N-cadherin localization, and actin cytoskeleton reorganization during cardiac chamber ballooning.
BACKGROUND: During heart morphogenesis, the cardiac chambers undergo ballooning: a process involving regionalized elongation of cardiomyocytes. Cardiomyocyte shape changes require reorganization of the actin cytoskeleton; however, the genetic regulation of this process is not well understood. RESULTS: 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-localization with RFP-Rab11a confirmed increased N-cadherin-positive recycling endosomes, demonstrating N-cadherin trafficking is perturbed in myo5b mutants. Finally, phalloidin staining showed disorganized F-actin in myo5b cardiomyocytes, suggesting the cytoskeleton fails to remodel, obstructing chamber ballooning. CONCLUSIONS: MyoVb is required for cardiomyocyte endosomal recycling and appropriate N-cadherin localization during the onset of chamber ballooning. Cardiomyocytes lacking MyoVb are unable to reorganize their actin cytoskeleton, resulting in failed chamber ballooning. Developmental Dynamics 248:284-295, 2019.
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Grassini et al. (2019) studied Cardiac chamber ballooning defects. myo5b mutation vs. Wild-type was evaluated on Cardiac chamber ballooning and N-cadherin trafficking. MyoVb mutation disrupts cardiomyocyte endosomal recycling and N-cadherin localization, preventing actin cytoskeleton reorganization and resulting in failed cardiac chamber ballooning.
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