3 years ago

Stat3 mediated alterations in lysosomal membrane protein composition.

Julie A Howard, Caroline C Krueger, Kathryn S Lilley, Michael E D'Angelo, Christine J Watson, Renata Feret, Michael J Deery, Bethan Lloyd-Lewis, Timothy J Sargeant
Lysosome function is essential in cellular homeostasis. In addition to its recycling role, the lysosome has recently been recognised as a cellular signalling 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 have 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 co-ordinately regulate endocytosis, intracellular trafficking and lysosome biogenesis to drive lysosomal-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.

Publisher URL: http://doi.org/10.1074/jbc.RA118.001777

DOI: 10.1074/jbc.RA118.001777

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