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PMID:18665841

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Citation

Radtke, AL and O'Riordan, MX (2008) Homeostatic maintenance of pathogen-containing vacuoles requires TBK1-dependent regulation of aquaporin-1. Cell. Microbiol. 10:2197-207

Abstract

Membranes are an integral component of many cellular functions and serve as a barrier to keep pathogenic bacteria from entering the nutrient-rich host cytosol. TANK-binding-kinase-1 (TBK1), a kinase of the IkappaB kinase family, is required for maintaining integrity of pathogen-containing vacuoles (PCV) upon bacterial invasion of host cells. Here we investigate how vacuolar integrity is maintained during bacterial infection, even in the presence of bacterial membrane damaging agents. We found that Aquaporin-1 (AQP1), a water channel that regulates swelling of secretory vesicles, associated with PCV. AQP1 levels were elevated in TBK1-deficient cells, and overexpression of AQP1 in wild-type cells led to PCV destabilization, similar to that observed in tbk1(-/-) cells. Inhibition of physiological levels of AQP1 in multiple cell types also led to increased instability of PCV, demonstrating a need for tightly regulated AQP1 function to maintain vacuole homeostasis during bacterial infection. AQP1-dependent modulation of PCV was triggered by bacterially induced membrane damage and ion flux. These results highlight the contribution of water channels to promoting PCV membrane integrity, and reveal an unexpected role for TBK1 and AQP1 in restricting bacterial pathogens to the vacuolar compartment.

Links

PubMed Online version:10.1111/j.1462-5822.2008.01199.x

Keywords

Animals; Aquaporin 1/genetics; Aquaporin 1/metabolism; Cell Membrane/metabolism; Cell Membrane/pathology; Fibroblasts/cytology; Fibroblasts/metabolism; Fibroblasts/microbiology; HeLa Cells; Homeostasis; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Vacuoles/metabolism; Vacuoles/microbiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:AQP1

involved_in

GO:0050829: defense response to Gram-negative bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AQP1

involved_in

GO:0050829: defense response to Gram-negative bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TBK1

involved_in

GO:0010629: negative regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AQP1

involved_in

GO:0085018: maintenance of symbiont-containing vacuole by host

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AQP1

colocalizes_with

GO:0020005: symbiont-containing vacuole membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:AQP1

involved_in

GO:0006813: potassium ion transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AQP1

enables

GO:0015079: potassium ion transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:AQP1

involved_in

GO:0085018: maintenance of symbiont-containing vacuole by host

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:AQP1

part_of

GO:0020003: symbiont-containing vacuole

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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