In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration
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.
Data availability
RNA-seq data were deposited at GEO with the data identifier GSE168371. BioID2 raw MS proteomics datasets have been deposited to MassIVE with the data identifier MSV000087028.
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RNA-seq from Pronobis et al.NCBI Gene Expression Omnibus, GSE168371.
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MS proteomics from Pronobis et al.MassIVE, MSV000087028.
Article and author information
Author details
Funding
Life Sciences Research Foundation
- Mira I Pronobis
National Heart, Lung, and Blood Institute (R35 HL150713)
- Kenneth D Poss
American Heart Association
- Kenneth D Poss
Fondation Leducq
- Kenneth D Poss
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Procedures involving animals were approved by the Institutional Animal Care and Use Committee at Duke University, Protocol number A005-21-01.
Reviewing Editor
- Lilianna Solnica-Krezel, Washington University School of Medicine, United States
Version history
- Received: December 29, 2020
- Accepted: March 25, 2021
- Accepted Manuscript published: March 25, 2021 (version 1)
- Version of Record published: April 9, 2021 (version 2)
Copyright
© 2021, Pronobis et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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