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Cell. 2015 Jun 4;161(6):1306-19. doi: 10.1016/j.cell.2015.05.009. Epub 2015 May 28.

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

Author information

1
Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
2
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
3
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
4
Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA; Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore. Electronic address: soman.abraham@duke.edu.

Abstract

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.

PMID:
26027738
PMCID:
PMC4458218
DOI:
10.1016/j.cell.2015.05.009
[Indexed for MEDLINE]
Free PMC Article

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