Deciphering intercellular signaling complexes by interaction-guided chemical proteomics

Zheng，Jiangnan1; Zheng，Zhendong1,2; Fu，Changying1; Weng，Yicheng1; He，An1; Ye，Xueting1; Gao，Weina1; Tian，Ruijun1,3

2023-12-01

10.1038/s41467-023-39881-9

Nature Communications   Impact Factor & Quartile

2041-1723

Indirect cell–cell interactions mediated by secreted proteins and their plasma membrane receptors play essential roles for regulating intercellular signaling. However, systematic profiling of the interactions between living cell surface receptors and secretome from neighboring cells remains challenging. Here we develop a chemical proteomics approach, termed interaction-guided crosslinking (IGC), to identify ligand-receptor interactions in situ. By introducing glycan-based ligation and click chemistry, the IGC approach via glycan-to-glycan crosslinking successfully captures receptors from as few as 0.1 million living cells using only 10 ng of secreted ligand. The unparalleled sensitivity and selectivity allow systematic crosslinking and identification of ligand-receptor complexes formed between cell secretome and surfaceome in an unbiased and all-to-all manner, leading to the discovery of a ligand-receptor interaction between pancreatic cancer cell-secreted urokinase (PLAU) and neuropilin 1 (NRP1) on pancreatic cancer-associated fibroblasts. This approach is thus useful for systematic exploring new ligand-receptor pairs and discovering critical intercellular signaling events.

SCI

English

NI Journal Papers ; NI论文

First ; Corresponding

Natural Science Foundation of Guangdong Province[2019B151502050];Ministry of Science and Technology of the People's Republic of China[2020YFE0202200];Ministry of Science and Technology of the People's Republic of China[2021YFA1301601];Ministry of Science and Technology of the People's Republic of China[2021YFA1301602];Ministry of Science and Technology of the People's Republic of China[2021YFA1302603];Ministry of Science and Technology of the People's Republic of China[2022YFC3401104];National Natural Science Foundation of China-Yunnan Joint Fund[22125403];National Natural Science Foundation of China-Yunnan Joint Fund[32171433];National Natural Science Foundation of China-Yunnan Joint Fund[32201218];National Natural Science Foundation of China-Yunnan Joint Fund[91953118];National Natural Science Foundation of China-Yunnan Joint Fund[and 22104047];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20200109140814408];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20200109141212325];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20210324120210029];

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001029450400021

NATURE PORTFOLIO

2-s2.0-85165293183

Scopus

1.Department of Chemistry,School of Science,Southern University of Science and Technology,Shenzhen,518055,China
2.School of Environment,Harbin Institute of Technology,Harbin,150090,China
3.Research Center for Chemical Biology and Omics Analysis,School of Science,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Road,518055,China

Zheng，Jiangnan,Zheng，Zhendong,Fu，Changying,et al. Deciphering intercellular signaling complexes by interaction-guided chemical proteomics[J]. Nature Communications,2023,14(1).

Zheng，Jiangnan.,Zheng，Zhendong.,Fu，Changying.,Weng，Yicheng.,He，An.,...&Tian，Ruijun.(2023).Deciphering intercellular signaling complexes by interaction-guided chemical proteomics.Nature Communications,14(1).

Zheng，Jiangnan,et al."Deciphering intercellular signaling complexes by interaction-guided chemical proteomics".Nature Communications 14.1(2023).