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Publication : A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion.

First Author  Miao Y Year  2015
Journal  Cell Volume  161
Issue  6 Pages  1306-19
PubMed ID  26027738 Mgi Jnum  J:223390
Mgi Id  MGI:5648763 Doi  10.1016/j.cell.2015.05.009
Citation  Miao Y, et al. (2015) A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion. Cell 161(6):1306-19
abstractText  Vertebrate cells have evolved elaborate cell-autonomous defense programs to monitor subcellular compartments for infection and to evoke counter-responses. These programs are activated by pathogen-associated pattern molecules and by various strategies intracellular pathogens employ to alter cellular microenvironments. Here, we show that, when uropathogenic E. coli (UPEC) infect bladder epithelial cells (BECs), they are targeted by autophagy but avoid degradation because of their capacity to neutralize lysosomal pH. This change is detected by mucolipin TRP channel 3 (TRPML3), a transient receptor potential cation channel localized to lysosomes. TRPML3 activation then spontaneously initiates lysosome exocytosis, resulting in expulsion of exosome-encased bacteria. These studies reveal a cellular default system for lysosome homeostasis that has been co-opted by the autonomous defense program to clear recalcitrant pathogens.
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