In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

eLife

Joseph A Goldman¹  Susan Zheng²  Kenneth D Poss³  Mira I Pronobis³  Sumeet Pal Singh⁴ 

[1] Department of Biological Chemistry and Pharmacology, The Ohio State University Medical Center, Columbus, United States;Department of Cell Biology, Duke University Medical Center, Durham, United States;Department of Cell Biology, Duke University Medical Center, Durham, United States;Regeneration Next, Duke University, Durham, United States;IRIBHM, Université Libre de Bruxelles (ULB), Brussels, Belgium;

关键词: BioID2;    heart regeneration;    proximity labeling;    ErbB2;    Rho A;    Zebrafish;   

DOI  :  10.7554/eLife.66079

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY