Stat3-mediated alterations in lysosomal membrane protein composition

Bethan Lloyd-Lewis, Caroline C Krueger, Timothy J Sargeant, Michael E D'Angelo, Michael J Deery, Renata Feret, Julie A Howard, Kathryn S Lilley, Christine J Watson

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Abstract

Lysosome function is essential in cellular homeostasis. In addition to its recycling role, the lysosome has recently been recognized as a cellular signaling hub. We have shown in mammary epithelial cells, both in vivo and in vitro, that signal transducer and activator of transcription 3 (Stat3) modulates lysosome biogenesis and can promote the release of lysosomal proteases that culminates in cell death. To further investigate the impact of Stat3 on lysosomal function, we conducted a proteomic screen of changes in lysosomal membrane protein components induced by Stat3 using an iron nanoparticle enrichment strategy. Our results show that Stat3 activation not only elevates the levels of known membrane proteins but results in the appearance of unexpected factors, including cell surface proteins such as annexins and flotillins. These data suggest that Stat3 may coordinately regulate endocytosis, intracellular trafficking, and lysosome biogenesis to drive lysosome-mediated cell death in mammary epithelial cells. The methodologies described in this study also provide significant improvements to current techniques used for the purification and analysis of the lysosomal proteome.

Original languageEnglish
Pages (from-to)4244-4261
Number of pages18
JournalJournal of Biological Chemistry
Volume293
Issue number12
Early online date17 Jan 2018
DOIs
Publication statusPublished - 23 Mar 2018

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Keywords

  • Animals
  • Cell Death
  • Cells, Cultured
  • Epithelial Cells/cytology
  • Female
  • Intracellular Membranes/metabolism
  • Lysosome-Associated Membrane Glycoproteins/metabolism
  • Lysosomes/metabolism
  • Mammary Glands, Animal/cytology
  • Proteome/metabolism
  • Proteomics
  • STAT3 Transcription Factor/metabolism
  • Signal Transduction

Cite this

Lloyd-Lewis, B., Krueger, C. C., Sargeant, T. J., D'Angelo, M. E., Deery, M. J., Feret, R., Howard, J. A., Lilley, K. S., & Watson, C. J. (2018). Stat3-mediated alterations in lysosomal membrane protein composition. Journal of Biological Chemistry, 293(12), 4244-4261. https://doi.org/10.1074/jbc.RA118.001777