We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Molecular basis of early epithelial response to streptococcal exotoxin: role of STIM1 and Orai1 proteins.
- Authors
Usmani, Shariq M.; von Einem, Jens; Frick, Manfred; Miklavc, Pika; Mayenburg, Martina; Husmann, Matthias; Dietl, Paul; Wittekindt, Oliver H.
- Abstract
Summary Streptolysin O (SLO) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pyogenes. SLO induces diverse types of Ca2+ signalling in host cells which play a key role in membrane repair and cell fate determination. The mechanisms behind SLO-induced Ca2+ signalling remain poorly understood. Here, we show that in NCI-H441 cells, wild-type SLO as well as non-pore-forming mutant induces long-lasting intracellular Ca2+ oscillations via IP3-mediated depletion of intracellular stores and activation of store-operated Ca2+ (SOC) entry. SLO-induced activation of SOC entry was confirmed by Ca2+ add-back experiments, pharmacologically and by overexpression as well as silencing of STIM1 and Orai1 expression. SLO also activated SOC entry in primary cultivated alveolar type II (ATII) cells but Ca2+ oscillations were comparatively short-lived in nature. Comparison of STIM1 and Orai1 revealed a differential expression pattern in H441 and ATII cells. Overexpression of STIM1 and Orai1 proteins in ATII cells changed the short-lived oscillatory response into a long-lived one. Thus, we conclude that SLO-mediated Ca2+ signalling involves Ca2+ release from intracellular stores and STIM1/Orai1-dependent SOC entry. The phenotype of Ca2+ signalling depends on STIM1 and Orai1 expression levels. Our findings suggest a new role for SOC entry-associated proteins in S. pyogenes-induced lung infection and pneumonia.
- Subjects
STREPTOCOCCUS pyogenes; EPITHELIAL cells; STREPTOLYSIN; CHOLESTEROL; MOLECULAR biology; CELL membranes; PNEUMONIA; BACTERIAL proteins
- Publication
Cellular Microbiology, 2012, Vol 14, Issue 3, p299
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/j.1462-5822.2011.01724.x