Role of calcium signalling and phosphorylations in disruption of the epithelial junctions by Pseudomonas aeruginosa quorum sensing molecule
2010 (English)In: European Journal of Cell Biology, ISSN 0171-9335, E-ISSN 1618-1298, Vol. 89, no 8, 584-597 p.Article in journal (Refereed) Published
In Pseudomonas aeruginosa. cell-cell communication based on acyl-homoserine lactone (HSL) quorum sensing molecules is known to coordinate the production of virulence factors and biofilms by the bacterium. Incidentally, these bacterial signals can also modulate mammalian cell behaviour. We demonstrate here that 3O-C-12-HSL can induce changes in calcium signalling through influx and release of calcium from thapsigargin-sensitive stores and delocalization of inositol 1,4,5-trisphosphate receptors (IP3R), but not of ryanodine receptors (RyR). In parallel, P. aeruginosa 3O-C-12-HSL disrupts junctions in human Caco-2 cells as evidenced by a reduction of the expression and distribution of ZO-3 and JAM-A. Using co-immunoprecipitation we also found an alteration in the binding of ZO-3 to JAM-A in protein complexes. Moreover, 3O-C-12-HSL-treatment resulted in tyrosine hyperphosphorylation of ZO-3 and JAM-A. On the contrary, serine and threonine residues of ZO-1 and JAM-A became less phosphorylated after exposition of 3O-C-12-HSL. The 3O-C-12-HSL-induced intracellular calcium signalling and alteration in the phosphorylation status of junction proteins furthermore correlated with changes in the association between JAM-A-ZO-3. The calcium inhibitors thapsigargin, xestospongin C. and dantrolene partly prevented the 3O-C-12-HSL-induced decreases in TER and increases in the paracellular flux of 10 kDa dextran. These findings clearly suggest that P. aeruginosa 3O-C-12-HSL can cause the loss of epithelial barrier function via calcium signalling and further alteration in the phosphorylation status of junction proteins; and that bacterial quorum sensing signals represent inter-kingdom signalling.
Place, publisher, year, edition, pages
Elsevier Science B. V., Amsterdam , 2010. Vol. 89, no 8, 584-597 p.
Quorum sensing; Pseudomonas aeruginosa; Acyl-homoserine lactone; Epithelial barrier; Tight junctions; Calcium signalling; Protein; phosphorylations/dephosphorylations
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-58236DOI: 10.1016/j.ejcb.2010.03.002ISI: 000279666100002OAI: oai:DiVA.org:liu-58236DiVA: diva2:338000