Key result
In vivo proximity labeling in zebrafish identified cardiomyocyte protein networks during heart regeneration, revealing that Rho A interacts with ErbB2 and its inhibition reduces cardiomyocyte proliferation by approximately 68%.
Why the study?
Strategies have not been available until recently to uncover interacting protein networks specific to key cell types, subcellular compartments, and major regulators during complex in vivo events.
In vivo proximity labeling with BioID2 successfully maps cardiomyocyte protein networks during zebrafish heart regeneration, identifying Rho A as a critical downstream effector of ErbB2 signaling required for cardiomyocyte proliferation.
Answers are grounded in this paper and cite their sources.
RhoA-ErbB2 interaction merits targeted study in regeneration models; leaves open translation beyond zebrafish.
Strategies have not been available until recently to uncover interacting protein networks specific to key cell types, their subcellular compartments, and their major regulators during complex in vivo events. Here we apply BioID2 proximity labeling to capture protein networks acting within cardiomyocytes during a key model of innate heart regeneration in zebrafish. Transgenic zebrafish expressing a promiscuous BirA2 localized to the entire myocardial cell or membrane compartment were generated, each identifying unique proteomes in adult cardiomyocytes that became altered during regeneration. BioID2 profiling for interactors with ErbB2, a co-receptor for the cardiomyocyte mitogen Nrg1, implicated Rho A as a target of ErbB2 signaling in cardiomyocytes. Blockade of Rho A during heart regeneration, or during cardiogenic stimulation by the mitogenic influences Nrg1, Vegfaa or Vitamin D, disrupted muscle creation. Our findings reveal proximity labeling as a useful resource to interrogate cell proteomes and signaling networks during tissue regeneration in zebrafish.
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Pronobis et al. (2021) studied Heart regeneration. BioID2 proximity labeling and Rho A inhibition (Rhosin) vs. Uninjured hearts or vehicle control was evaluated on Cardiomyocyte protein network changes and proliferation index. In vivo proximity labeling in zebrafish identified cardiomyocyte protein networks during heart regeneration, revealing that Rho A interacts with ErbB2 and its inhibition reduces cardiomyocyte proliferation by approximately 68%.
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