Molecular mechanism of protrusion formation during cell-to-cell spread of Listeria.

[wiskott-aldrich syndrome]

The bacterial pathogen Listeria monocytogenes spreads within human tissues using a motility process dependent on the host actin cytoskeleton . Cell-to -cell spread involves the ability of motile bacteria to remodel the host plasma membrane into protrusions , which are internalized by neighboring cells . Recent results indicate that formation of Listeria protrusions in polarized human cells involves bacterial antagonism of a host signaling pathway comprised of the scaffolding protein Tuba and its effectors N-WASP and Cdc 42 . These three human proteins form a complex that generates tension at apical cell junctions . Listeria relieves this tension and facilitates protrusion formation by secreting a protein called InlC . InlC interacts with a Src Homology 3 (SH 3 ) domain in Tuba , thereby displacing N-WASP from this domain . Interaction of InlC with Tuba is needed for efficient Listeria spread in cultured human cells and infected animals . Recent structural data has elucidated the mechanistic details of InlC /Tuba interaction , revealing that InlC and N-WASP compete for partly overlapping binding surfaces in the Tuba SH 3 domain . InlC binds this domain with higher affinity than N-WASP , explaining how InlC is able to disrupt Tuba /N-WASP complexes .