MACSPI enables tissue- selective proteomic and interactomic analyses in multicellular organisms

• 成果类型: Article
• 署名作者: Huang, Siyue; Ran, Qiao; Li, Xiao-Meng; Bao, Xiucong; Zheng, Chaogu; Li, Xiang David
• 署名单位: University of Hong Kong; University of Hong Kong; University of Hong Kong
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15163
• DOI: 10.1073/pnas.2319060121
• 发表日期: 2024-05-21
• 关键词: amino-acid; chaperone; proteins; tool; DISCOVERY; efficient; unc-45; myosin; map

摘要

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog - based Cell - Specific Proteomics and Interactomics (MACSPI). This method uses the tissue - specific expression of an engineered methionyl - tRNA synthetase to label proteins with a bifunctional amino acid 2 - amino - 5 - diazirinylnonynoic acid in selected cells. We applied MACSPI in Caenorhabditis elegans, a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue - specific proteins. Using the photo - cross - linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue - specific interactors and stress - related interactors. Our study demonstrates that MACSPI can be used to profile tissue - specific proteomes and interactomes in intact multicellular organisms.