Chemical proteomics reveals post-translational remodeling of endosomal pathways during macrophage activation.
- 1The Rockefeller University
Abstract
Macrophages are central regulators of innate immunity, yet the post-translational mechanisms that enable rapid inflammatory responses remain incompletely understood. Here, we integrated transcriptomics, unenriched proteomics, phosphoproteomics, metabolomics, and cysteine reactivity profiling to comprehensively characterize primary human macrophages following Toll-like receptor and Stimulator of Interferon Genes (STING) activation. This approach revealed substantial discordance between transcript- and protein-level changes, as well as extensive post-translational remodeling. Differentially reactive cysteines were enriched in proteins involved in small-GTPase signaling, vesicular trafficking, and the endo-lysosomal system. Reactivity changes in two subunits of the endosomal mRNA-transport FERRY complex nominated it as a candidate target of inflammation-associated post-translational regulation. Biochemical and imaging analyses established FERRY complex assembly and early endosomal localization in primary human macrophages and identified DISC1 as a previously unrecognized FERRY-associated protein. This work provides a comprehensive resource of biochemical and post-translational remodeling during macrophage activation and implicates endosome-associated mRNA transport in innate immune regulation.
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BibTeX
@misc{zhang2026chemical,
title = {{Chemical proteomics reveals post-translational remodeling of endosomal pathways during macrophage activation.}},
author = {T. L. Zhang and H. Sanford and R. R. Gabbasova and A. E. van Vlimmeren and Y. Kalaidzidis and H. Kojima and C. R. Wayne and J. Biswas and P. Banerjee and B. Zhang and O. Abdel-Wahab and M. Zerial and E. V. Vinogradova},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754469},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754469v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Chemical proteomics reveals post-translational remodeling of endosomal pathways during macrophage activation.
AU - T. L. Zhang
AU - H. Sanford
AU - R. R. Gabbasova
AU - A. E. van Vlimmeren
AU - Y. Kalaidzidis
AU - H. Kojima
AU - C. R. Wayne
AU - J. Biswas
AU - P. Banerjee
AU - B. Zhang
AU - O. Abdel-Wahab
AU - M. Zerial
AU - E. V. Vinogradova
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754469
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754469v1
AB - Macrophages are central regulators of innate immunity, yet the post-translational mechanisms that enable rapid inflammatory responses remain incompletely understood. Here, we integrated transcriptomics, unenriched proteomics, phosphoproteomics, metabolomics, and cysteine reactivity profiling to comprehensively characterize primary human macrophages following Toll-like receptor and Stimulator of Interferon Genes (STING) activation. This approach revealed substantial discordance between transcript- and protein-level changes, as well as extensive post-translational remodeling. Differentially reactive cysteines were enriched in proteins involved in small-GTPase signaling, vesicular trafficking, and the endo-lysosomal system. Reactivity changes in two subunits of the endosomal mRNA-transport FERRY complex nominated it as a candidate target of inflammation-associated post-translational regulation. Biochemical and imaging analyses established FERRY complex assembly and early endosomal localization in primary human macrophages and identified DISC1 as a previously unrecognized FERRY-associated protein. This work provides a comprehensive resource of biochemical and post-translational remodeling during macrophage activation and implicates endosome-associated mRNA transport in innate immune regulation.
ER -