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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Miao, Y; Li, G; Zhang, X; Xu, H; Abraham, SN

Published Date

  • June 4, 2015

Published In

Volume / Issue

  • 161 / 6

Start / End Page

  • 1306 - 1319

PubMed ID

  • 26027738

Pubmed Central ID

  • 26027738

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2015.05.009

Language

  • eng

Conference Location

  • United States