Biology Reference
In-Depth Information
precursor (LRP) interacted with the N-terminal CNF1 and full-length CNF1
but not with the C-terminal CNF1. CNF1-mediated RhoA activation and bac-
terial uptake were inhibited by LRP antisense oligodeoxynucleotides,whereas
they were increased in LRP-overexpressing cells, demonstrating correlation
between effects of CNF1 and levels of LRP expression in HBMEC ( Chung
et al., 2003 ). These findings indicate that CNF1 interaction with its receptor,
LRP, is the initial step required for CNF1-mediated RhoA activation and bac-
terial uptake in eukaryotic cells. The 37-kDa LRP is a ribosome-associated
cytoplasmic protein and shown to be a precursor of 67-kDa laminin receptor
(67 LR). It is unclear how 67 LR is matured and synthesized from the LRP,
but mature 67 LR is shown to be present on the cell surface and functions as
a membrane receptor for the adhesive basement membrane protein laminin
( Massia et al., 1993 ). We have shown that incubation of HBMEC with CNF1-
expressing E. coli K1 up-regulates 67 LR expression and recruits 67 LR to the
site of invading E. coli K1 in a CNF1-dependent manner ( Kim et al., 2003 ),
supporting the participation of 67 LR in CNF1-expressing E. coli K1 invasion
of HBMEC.
Of interest, LRP is also shown to be a cellular target for other CNS-infect-
ing microorganisms, including S. pneumoniae , N. meningitidis , H. influenzae
type b, dengue virus, adeno-associated virus, Venezuelan equine encephalitis
virus, and prion protein ( Table 10.3 ). The mechanisms by which the same
receptor is involved in CNS penetration by different organisms remain to be
established.
E. coli invasion of HBMEC involves host cell actin cytoskeleton
rearrangements
Pathogenic microbes exploit various strategies to penetrate into their host cells
( Knodler et al., 2001 ; Cossart and Sansonetti, 2004 ; Kim, 2008 ). Microbial
internalization into non-professional phagocytes such as endothelial and epi-
thelial cells is shown to occur mainly via two different mechanisms involv-
ing host cell actin cytoskeleton rearrangements: a zipper mechanism involving
the formation of cell protrusions in contact with the pathogens and a trigger
mechanism involving the formation of membrane ruffling around the pathogens
( Knodler et al., 2001 ; Cossart and Sansonetti, 2004 ).
Studies with scanning and transmission electron microscopy have shown
that internalization of meningitis-causing E. coli K1 into HBMEC is associ-
ated with microvilli-like protrusions at the entry site on the surface of HBMEC
( Nemani et al., 1999 ; Kim, 2003 ) ( Figure 10.1 ), suggesting the involvement of
host cell actin cytoskeleton rearrangement in E. coli K1 invasion of HBMEC.
This concept is supported by the demonstrations that F-actin condensation
occurs with invading bacteria and blockade of actin condensation with microfil-
ament-disrupting agents such as cytochalasin D inhibits E. coli K1 invasion of
HBMEC ( Nemani et al., 1999 ).
Search WWH ::




Custom Search