Abstract
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.
Highlights
Understanding how and why tissue regeneration occurs is a central objective of developmental biology
We show that BioID2 can be used to track changes in protein levels in whole cardiomyocytes or their membrane compartments during regeneration
We investigate the proximal proteome of ErbB2 in cardiomyocytes, finding an increase in association with the small GTPase Rho A during regeneration, a protein with activity we find to be essential for injury-induced regeneration and the proliferative response to mitogens
Summary
Understanding how and why tissue regeneration occurs is a central objective of developmental biology. Developmental Biology fewer have explored in vivo networks in mice or Drosophila (Spence et al, 2019; Feng et al, 2020; Rudolph et al, 2020; Mannix et al, 2019; Cho et al, 2020) In the latter studies, proximity labeling captured the proteome within interneuron–neuron interactions, within muscle sarcomeres, and in the ring canal of Drosophila oocytes, producing new insights into protein network assemblies and signaling. Our findings demonstrate the utility of proximity labeling as a resource to interrogate cell proteomes and signaling networks during tissue regeneration in zebrafish, and they identify a key role of small GTPases in injury-induced cardiogenesis
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