Key result
In vivo proximity labeling identified Rho A as a target of ErbB2 signaling, and blockade of Rho A reduced the cardiomyocyte proliferation index by approximately 68% during zebrafish heart regeneration.
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.
Answers are grounded in this paper and cite their sources.
In vivo proximity labeling using BioID2 in zebrafish identifies key cardiomyocyte protein networks, revealing Rho A as a crucial target of ErbB2 signaling for heart regeneration.
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 distinct 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. Rho A inhibition (Rhosin) vs. Vehicle was evaluated on Cardiomyocyte proliferation index (p=0.012). In vivo proximity labeling identified Rho A as a target of ErbB2 signaling, and blockade of Rho A reduced the cardiomyocyte proliferation index by approximately 68% during zebrafish heart regeneration.
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