Premium
IQGAP1 regulates actin pedestal formation by enteropathogenic E. coli
Author(s) -
Brown Matthew,
Bry Lynn,
Li Zhigang,
Sacks David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1030.1
Subject(s) - iqgap1 , microbiology and biotechnology , actin cytoskeleton , actin , lamellipodium , biology , mdia1 , cytoskeleton , cdc42 , wiskott–aldrich syndrome protein , chemistry , scaffold protein , signal transduction , cell , biochemistry
Microbial pathogens continue to be a major cause of morbidity and mortality worldwide. Many microbes utilize the host cell cytoskeleton for attachment, entry into cells, movement inside and between cells and vacuole formation. Enteropathogenic E. coli (EPEC) use a type three secretion system to inject into the host cell bacterial toxins, which act through N‐WASP and Arp2/3 to promote actin polymerization (Nat Rev Micro Hayward, 2006; 4:358). This localized polymerization of actin induces the formation of stable actin pedestals that support the EPEC. IQGAP1 is a widely expressed 190kDa protein that binds activated Cdc42 and Rac1 (but not RhoA or Ras), actin, calmodulin, E‐cadherin, β‐catenin, extracellular signal‐regulated kinase 1 (ERK1) and ERK2 (Trends Cell Biol. Brown, 2006; 16:242). A primary function of IQGAP1 is to modulate cytoskeletal architecture through a direct interaction with actin, and also indirectly through the RhoGTPases, Cdc42 and Rac1 and via N‐WASP. We show through immunocytochemistry and confocal microscopy IQGAP1 localises to EPEC‐induced actin pedestals. Analysis with selected IQGAP1 mutant constructs indicates IQGAP1 localises to these structures independently of its interactions with actin, Rac1/Cdc42 and calmodulin. Through immunoprecipitation of endogenous IQGAP1 and detecting co‐immunprecipitated proteins, we observe that infection of HeLa cells with EPEC promotes the interaction of IQGAP1 with calmodulin, concomitantly reducing the interaction of IQGAP1 with Rac1 and Cdc42. Together, these data identify IQGAP1 and calmodulin in a novel signaling pathway inducing actin pedestal formation by EPEC, and playing a role in EPEC pathogenicity.