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Actin-based motility of Intracellular Pathogens |
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| We are studying
three pathogens: Listeria monocytogenes, Shigella flexneri,
and Vaccinia which display the remarkable ability to reorganize the actin
cytoskeleton within host cells. These pathogens usurp the host cell's
contractile system to
promote it's own cell-to-cell transfer to evade humoral immunity. Host cell actin regulatory proteins are utilized to
stimulate the formation of rocket-tail structures that continually grow at
sites proximal to the bacterium or virion.
There is widespread interest in the underlying molecular mechanisms
underlying in Listeria, Shigella and Vaccinia motility because changes in
the cytoskeleton at the cell's leading edge also involves mechanistically
analogous interactions. Recent advances in our understanding of these
fundamental cytoskeletal rearrangements have been achieved through a clearer
recognition of the central role of oligo-proline sequence repeats present in
ActA,vinculin,and zyxin for generating an Actin-Based Motility
complex (ABM complex). The ABM complex attracts high concentrations of
profilin, a molecule that binds to actin monomers and stimulates actin
filament assembly required to form pseudopods and lamellipods at the
peripheral membrane.
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Listeria moving through PtK2 cell by actin-based motility. Green = actin
filament stain, Red = Listeria stain. Note the long actin filament tails
behind the moving bacteria. |
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