Dataset Information

Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks

ABSTRACT: Delineating the extracellular interaction network of the cell surface proteotype (the surfaceome) is fundamental to understanding cellular signaling function in health and disease. Here, we developed LUX-MS, an optoproteomic technology that enables the spatiotemporal and proteome-wide study of surfaceome signaling architectures at nanoscale level without the need for genetic manipulation. A tunable, light-triggered singlet oxygen generator (SOG) based mechanism mediates in-situ proximity-tagging for subsequent mass spectrometry-based identification of acute protein interactions in their native cellular context. We applied LUX-MS to the characterization of surfaceome signaling structures engaged by antibodies, small molecule drugs, biologics and intact bacteriophages across organisms and in complex environments. Cell-type resolved dissection of intercellular communication using LUX-MS thereby revealed the molecular architecture of functional immunological signaling synapses in unprecedented detail. Altogether, LUX-MS enables facebooking of the social protein networks within surfaceome signaling architectures and provides an unprecedented molecular framework for the rational design of biomedical intervention strategies.

INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Fusion, Q Exactive HF

ORGANISM(S): Listeria Phage A500 Homo Sapiens (human) Escherichia Coli Listeria Monocytogenes Serotype 4b Mus Musculus (mouse)

TISSUE(S): B Cell, Primary Cell, Blood Cell, Cell Suspension Culture, T Cell, Dendritic Cell, Cell Culture

DISEASE(S): Lymphoma

SUBMITTER: Maik Müller

LAB HEAD: Bernd Wollscheid

PROVIDER: PXD020481 | Pride | 2021-06-14

REPOSITORIES: Pride

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Publications

Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks.

Müller Maik M Gräbnitz Fabienne F Barandun Niculò N Shen Yang Y Wendt Fabian F Steiner Sebastian N SN Severin Yannik Y Vetterli Stefan U SU Mondal Milon M Prudent James R JR Hofmann Raphael R van Oostrum Marc M Sarott Roman C RC Nesvizhskii Alexey I AI Carreira Erick M EM Bode Jeffrey W JW Snijder Berend B Robinson John A JA Loessner Martin J MJ Oxenius Annette A Wollscheid Bernd B

Nature communications 20211202 1

The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer extracellular signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions ...[more]

PMID: 34857745

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Project description:Maternal antibodies specific for antigens in the developing brain are implicated as risk factors for neurodevelopmental disorders, but how these antibodies interfere with neurodevelopment remain speculative. It has been postulated that immunoglobulin G-immune complexes (IgG-IC) activate Fc gamma receptors (FcγR) on non-immune cells in the brain, thereby modulating intracellular signaling and/or internalizing function-blocking antibodies specific for intracellular antigens. However, testing this hypothesis has been hindered by the paucity of data regarding FcγR in the developing brain. Thus, we first investigated FcγR expression in the brain of neonatal male and female rats using quantitative PCR analyses. FcgrIa, FcgrIIa, FcgrIIb, FcgrIIIa and Fcgrt transcripts were detectable in the cortex, hippocampus and cerebellum at postnatal days 1 and 7. These transcripts were also present in primary hippocampal and cortical cell cultures, where their expression was upregulated by IFNγ. In order to confirm protein abundance of FcγRIa, FcγRIIb and FcγRIIIa in cultured hippocampal and cortical neurons and astrocytes on the single cell and tissue level we used immunocytochemistry, western blotting, proteotype analysis, and flow cytometry. The data shows that a subpopulation of these cells co-express the excitatory FcγRIa and the inhibitory FcγRIIb. Functional analysis shows that exposure of hippocampal and cortical cell cultures to IgG-IC increased intracellular calcium and Erk phosphorylation, and triggered FcγR-mediated internalization of IgG. Collectively, these data demonstrate that developing neurons and astrocytes express signaling competent FcγR. which could establish a molecular mode of action of maternal antibodies could influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR on non-immune cells in the developing brain. These findings support the hypothesis that maternal antibodies influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR on non-immune cells in the developing brain.

Dataset Information

Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks

Publications

Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks.

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