Generation of a deep mouse brain spectral library for transmembrane proteome profiling in mental disease models

Shanshan Li; Huoqing Luo; Pan Tang; Cuiping Tian; Ji Hu; Haojie Lu; Wenqing Shui

doi:10.1016/j.mcpro.2024.100777

Generation of a deep mouse brain spectral library for transmembrane proteome profiling in mental disease models

Mol Cell Proteomics. 2024 Apr 24:100777. doi: 10.1016/j.mcpro.2024.100777. Online ahead of print.

Authors

Shanshan Li¹, Huoqing Luo², Pan Tang³, Cuiping Tian⁴, Ji Hu⁵, Haojie Lu⁶, Wenqing Shui⁷

Affiliations

¹ Institutes of Biomedical Sciences and Department of Chemistry, Fudan University, Shanghai, 200032, China; iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
² School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China; Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
³ iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ iHuman Institute, ShanghaiTech University, Shanghai 201210, China.
⁵ School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: huji@shanghaitech.edu.cn.
⁶ Institutes of Biomedical Sciences and Department of Chemistry, Fudan University, Shanghai, 200032, China. Electronic address: luhaojie@fudan.edu.cn.
⁷ iHuman Institute, ShanghaiTech University, Shanghai 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: shuiwq@shanghaitech.edu.cn.

PMID: 38670310
DOI: 10.1016/j.mcpro.2024.100777

Abstract

Transmembrane (TM) proteins constitute over 30% of the mammalian proteome and play essential roles in mediating cell-cell communication, synaptic transmission and plasticity in the central nervous system. Many of these proteins, especially the G protein-coupled receptors (GPCRs), are validated or candidate drug targets for therapeutic development for mental diseases, yet their expression profiles are underrepresented in most global proteomic studies. Herein, we establish a brain TM protein-enriched spectral library based on 136 DDA runs acquired from various brain regions of both naïve mice and mental disease models. This spectral library comprises 3043 TM proteins including 171 GPCRs, 231 ion channels and 598 transporters. Leveraging this library, we analyzed the DIA data from different brain regions of two mouse models exhibiting depression- or anxiety-like behaviors. By integrating multiple informatics workflows and library sources, our study significantly expanded the mental stress-perturbed TM proteome landscape, from which a new GPCR regulator of depression was verified by in vivo pharmacological testing. In summary, we provide a high-quality mouse brain TM protein spectral library to largely increase the TM proteome coverage in specific brain regions, which would catalyze the discovery of new potential drug targets for the treatment of mental disorders.