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IQGAP1 mediates the disruption of adherens junctions to promote Escherichia coli K1 invasion of brain endothelial cells.


ABSTRACT: The transcellular entry of Escherichia coli K1 through human brain microvascular endothelial cells (HBMEC) is responsible for tight junction disruption, leading to brain oedema in neonatal meningitis. Previous studies demonstrated that outer membrane protein A (OmpA) of E.?coli K1 interacts with its receptor, Ecgp96, to induce PKC-? phosphorylation, adherens junction (AJ) disassembly (by dislodging ?-catenin from VE-cadherin), and remodelling of actin in HBMEC. We report here that IQGAP1 mediates ?-catenin dissociation from AJs to promote actin polymerization required for E.?coli K1 invasion of HBMEC. Overexpression of C-terminal truncated IQGAP1 (IQ?C) that cannot bind ?-catenin prevents both AJ disruption and E.?coli K1 entry. Of note, phospho-PKC-? interacts with the C-terminal portion of Ecgp96 as well as with VE-cadherin after IQGAP1-mediated AJ disassembly. HBMEC overexpressing either C-terminal truncated Ecgp96 (Ecgp96?200) or IQ?C upon infection with E.?coli showed no interaction of phospho-PKC-? with Ecgp96. These data indicate that the binding of OmpA to Ecgp96 induces PKC-? phosphorylation and association of phospho-PKC-? with Ecgp96, and then signals IQGAP1 to detach ?-catenin from AJs. Subsequently, IQGAP1/?-catenin bound actin translocates to the site of E.?coli K1 attachment to promote invasion.

SUBMITTER: Krishnan S 

PROVIDER: S-EPMC3410974 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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IQGAP1 mediates the disruption of adherens junctions to promote Escherichia coli K1 invasion of brain endothelial cells.

Krishnan Subramanian S   Fernandez G Esteban GE   Sacks David B DB   Prasadarao Nemani V NV  

Cellular microbiology 20120524 9


The transcellular entry of Escherichia coli K1 through human brain microvascular endothelial cells (HBMEC) is responsible for tight junction disruption, leading to brain oedema in neonatal meningitis. Previous studies demonstrated that outer membrane protein A (OmpA) of E. coli K1 interacts with its receptor, Ecgp96, to induce PKC-α phosphorylation, adherens junction (AJ) disassembly (by dislodging β-catenin from VE-cadherin), and remodelling of actin in HBMEC. We report here that IQGAP1 mediate  ...[more]

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