2. Academic Validation
  3. Quantitative and Dynamic Catalogs of Proteins Released during Apoptotic and Necroptotic Cell Death

Quantitative and Dynamic Catalogs of Proteins Released during Apoptotic and Necroptotic Cell Death

  • Cell Rep. 2020 Jan 28;30(4):1260-1270.e5. doi: 10.1016/j.celrep.2019.12.079.
Maria C Tanzer 1,  Annika Frauenstein 2,  Che A Stafford 3,  Kshiti Phulphagar 2,  Matthias Mann 4,  Felix Meissner 5
Affiliations

Affiliations

  • 1 Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
  • 2 Experimental Systems Immunology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
  • 3 Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
  • 4 Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany. Electronic address: mmann@biochem.mpg.de.
  • 5 Experimental Systems Immunology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany. Electronic address: meissner@biochem.mpg.de.
PMID: 31995763 DOI: 10.1016/j.celrep.2019.12.079
Abstract

The inflammatory functions of the cytokine tumor necrosis factor (TNF) rely on its ability to induce cytokine production and to induce cell death. Caspase-dependent and caspase-independent pathways-apoptosis and Necroptosis, respectively-regulate immunogenicity by the release of distinct sets of cellular proteins. To obtain an unbiased, systems-level understanding of this important process, we here applied mass spectrometry-based proteomics to dissect protein release during Apoptosis and Necroptosis. We report hundreds of proteins released from human myeloid cells in time course experiments. Both cell death types induce receptor shedding, but only apoptotic cells released nucleosome components. Conversely, necroptotic cells release lysosomal components by activating lysosomal exocytosis at early stages of necroptosis-induced membrane permeabilization and show reduced release of conventionally secreted cytokines.

Keywords

TNF; apoptosis; cytokine release; extracellular vesicles; lysosomal exocytosis; mass spectrometry; necroptosis; receptor shedding.

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