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Stat3-mediated alterations in lysosomal membrane protein composition.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Lloyd-Lewis, Bethan 
Krueger, Caroline C 
Sargeant, Timothy J 
D'Angelo, Michael E 
Deery, Michael J 

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.

Description

Keywords

STAT3, cell death, involution, lysosome, lysosome purification, mammary epithelial cells, mammary gland, proteomics, Animals, Cell Death, Cells, Cultured, Epithelial Cells, Female, Intracellular Membranes, Lysosomal Membrane Proteins, Lysosomes, Mammary Glands, Animal, Proteome, Proteomics, STAT3 Transcription Factor, Signal Transduction

Journal Title

J Biol Chem

Conference Name

Journal ISSN

0021-9258
1083-351X

Volume Title

293

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MR/J001023/1)