Stitching the synapse: Cross-linking mass spectrometry into resolving synaptic protein interactions

M. A. Gonzalez-Lozano, F. Koopmans, P. F. Sullivan, J. Protze, G. Krause, M. Verhage, K. W. Li*, F. Liu, A. B. Smit

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Synaptic transmission is the predominant form of communication in the brain. It requires functionally specialized molecular machineries constituted by thousands of interacting synaptic proteins. Here, we made use of recent advances in cross-linking mass spectrometry (XL-MS) in combination with biochemical and computational approaches to reveal the architecture and assembly of synaptic protein complexes from mouse brain hippocampus and cerebellum. We obtained 11,999 unique lysine-lysine cross-links, comprising connections within and between 2362 proteins. This extensive collection was the basis to identify novel protein partners, to model protein conformational dynamics, and to delineate within and between protein interactions of main synaptic constituents, such as Camk2, the AMPA-type glutamate receptor, and associated proteins. Using XL-MS, we generated a protein interaction resource that we made easily accessible via a web-based platform (http://xlink.cncr.nl) to provide new entries into exploration of all protein interactions identified.

Original languageEnglish
Article numbereaax5783
JournalScience advances
Volume6
Issue number8
DOIs
Publication statusPublished - 1 Jan 2020

Funding

M.A.G.-L. was funded by EU-FP7 MC-ITN IN-SENS (no. 607616) and the Schizophrenia United Network (SUN) project. We acknowledge support from the Swedish Research Council (Vetenskapsr?det, award D0886501). F.L.?s work was supported by the Leibniz Association with the Leibniz-Wettbewerbs and by the Netherlands Organization for Scientific Research (NWO) through funding of the large-scale proteomics facility Proteins@ Work (project 184.032.201) embedded in the Netherlands Proteomics Centre.

FundersFunder number
Netherlands Proteomics Centre
Schizophrenia United Network
Seventh Framework Programme607616
Leibniz-Gemeinschaft
Nederlandse Organisatie voor Wetenschappelijk Onderzoek184.032.201
VetenskapsrådetD0886501
Seventh Framework Programme

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