%0 Journal Article
%T Gap-Junction-Dependent Labeling of Nascent Proteins in Multicellular Networks
%J -
%D 2019
%R https://doi.org/10.1021/acschembio.8b01065
%X Intercellular communication via gap junctions is crucial for orchestrating behaviors of multicellular systems. Imaging methods and electrophysiological techniques have been widely used to identify gap junctions and map the gap-junction-connected cell networks. However, analyzing gene expression within a gap-junction network remains challenging. Herein, we report the development of bio-orthogonal recording of translation in adjacent cells connected by gap junctions (BORTAC-GJ), a gap-junction-dependent protein tagging method based on local activation of clickable amino acid analogues that pass through gap junctions and are metabolically incorporated into nascent proteins. We demonstrated that BORTAC-GJ enabled selective labeling of nascent proteomes, thus recording translation, in cell networks connected by gap junctions, leaving unconnected cells not labeled. We further applied BORTAC-GJ to probe bystander STING activation triggered by gap-junction-mediated cGAMP transfer, an important process in innate immune response. BORTAC-GJ provides a means to investigate the gap-junction network at the proteome level and is broadly applicable for various cell types connected by gap junctions
%U https://pubs.acs.org/doi/10.1021/acschembio.8b01065