Spatiotemporal proteomic profiling of the pro-inflammatory response to lipopolysaccharide in the THP-1 human leukaemia cell line.

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Ribeiro, Andre LR 

Protein localisation and translocation between intracellular compartments underlie almost all physiological processes. The hyperLOPIT proteomics platform combines mass spectrometry with state-of-the-art machine learning to map the subcellular location of thousands of proteins simultaneously. We combine global proteome analysis with hyperLOPIT in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during a lipopolysaccharide (LPS)-induced inflammatory response. We report a highly dynamic proteome in terms of both protein abundance and subcellular localisation, with alterations in the interferon response, endo-lysosomal system, plasma membrane reorganisation and cell migration. Proteins not previously associated with an LPS response were found to relocalise upon stimulation, the functional consequences of which are still unclear. By quantifying proteome-wide uncertainty through Bayesian modelling, a necessary role for protein relocalisation and the importance of taking a holistic overview of the LPS-driven immune response has been revealed. The data are showcased as an interactive application freely available for the scientific community.

Algorithms, Anti-Infective Agents, Anti-Inflammatory Agents, Antigen Presentation, Autophagosomes, Bayes Theorem, Cell Cycle Checkpoints, Cell Membrane, Cell Nucleus, Cell Shape, Humans, Immunity, Inflammation, Leukemia, Lipopolysaccharides, Lymphocyte Activation, Lysosomes, Neoplasm Proteins, Protein Transport, Proteome, Proteomics, Signal Transduction, T-Lymphocytes, THP-1 Cells, Time Factors, Transport Vesicles, Up-Regulation, rho GTP-Binding Proteins
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Nat Commun
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Springer Science and Business Media LLC
Wellcome Trust (108467/Z/15/Z)
Wellcome Trust (110170/Z/15/Z)
Wellcome Trust (108441/Z/15/Z)
European Commission Horizon 2020 (H2020) Research Infrastructures (RI) (823839)
Wellcome Trust (099135/Z/12/Z)
Wellcome Trust (110071/Z/15/Z)
Biotechnology and Biological Sciences Research Council (BB/H024247/1)
Biotechnology and Biological Sciences Research Council (BB/K00137X/1)
Biotechnology and Biological Sciences Research Council (BB/N023129/1)
EU Horizon 2020 program INFRAIA project Epic‐XS (Project 823839)