Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris

Brian Scharf, Cristina C. Clement, Xiao Xuan Wu, Kateryna Morozova, Diego Zanolini, Antonia Follenzi, Jorge N. Larocca, Kalle Levon, Fayyaz S. Sutterwala, Jacob Rand, Neil Cobelli, Ed Purdue, Katherine A. Hajjar, Laura Santambrogio

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26 Scopus citations

Abstract

Endosomal functions are contingent on the integrity of the organelle-limiting membrane, whose disruption induces inflammation and cell death. Here we show that phagocytosis of ultrahigh molecular weight polyethylene particles induces damage to the endosomal-limiting membrane and results in the leakage of cathepsins into the cytosol and NLRP3-inflammasome activation. Annexin A2 recruitment to damaged organelles is shown by two-dimensional DIGE protein profiling, endosomal fractionation, confocal analysis of endogenous and annexin A2-GFP transfected cells, and immunogold labelling. Binding experiments, using fluorescent liposomes, confirms annexin A2 recruitment to endosomes containing phagocytosed polyethylene particles. Finally, an increase in cytosolic cathepsins, NLRP3-inflammasome activation, and IL-1 production is seen in dendritic cells from annexin A2-null mice, following exposure to polyethylene particles. Together, the results indicate a functional role of annexin A2 binding to endosomal membranes following organelle destabilization.

Original languageEnglish (US)
Article number755
JournalNature communications
Volume3
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Scharf, B., Clement, C. C., Wu, X. X., Morozova, K., Zanolini, D., Follenzi, A., Larocca, J. N., Levon, K., Sutterwala, F. S., Rand, J., Cobelli, N., Purdue, E., Hajjar, K. A., & Santambrogio, L. (2012). Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris. Nature communications, 3, [755]. https://doi.org/10.1038/ncomms1754