Involvement of CD44v6 in InlB-dependent Listeria invasion.
Listeria monocytogenes, a Gram-positive bacterium, is the causative agent for the disease called listeriosis. This pathogen utilizes host cell surface proteins such as E-cadherin or c-Met in order to invade eukaryotic cells. The invasion via c-Met depends on the bacterial protein InlB that activates c-Met phosphorylation and internalization mimicking in many regards HGF, the authentic c-Met ligand. In this paper, we demonstrate that the activation of c-Met induced by InlB is dependent on CD44v6, a member of the CD44 family of transmembrane glycoproteins. Inhibiting CD44v6 by means of a blocking peptide, a CD44v6 antibody or CD44v6-specific siRNA prevents the activation of c-Met induced by InlB. Subsequently, signalling, scattering and the entry of InlB-coated beads into host cells are also impaired by CD44v6 blocking reagents. For the entry process, ezrin, a protein that links the CD44v6 cytoplasmic domain to the cytoskeleton, is required as well. Most importantly, this collaboration between c-Met and CD44v6 contributes to the invasion of L. monocytogenes into target cells as demonstrated by a drastic decrease in bacterial invasion in the presence of blocking agents such as the CD44v6 peptide or antibody.
Jung
C
C
Forschungszentrum Karlsruhe, Institute for Toxicology and Genetics, Postfach 3640, 76021 Karlsruhe, Germany.
Matzke
A
A
Niemann
H H
HH
Schwerk
Christian
C
Tenenbaum
Tobias
T
Orian-Rousseau
V
V
D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D000099149:Ezrin
D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D019859:Proto-Oncogene Proteins c-met; D000099149:Ezrin; C112697:CD44v6 antigen; C095768:inlB protein, Listeria monocytogenes