Involvement of CD44v6 in InlB-dependent Listeria invasion |
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Authors: | C. Jung A. Matzke H. H. Niemann Christian Schwerk Tobias Tenenbaum V. Orian-Rousseau |
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Affiliation: | Forschungszentrum Karlsruhe, Institute for Toxicology and Genetics, Postfach 3640, 76021 Karlsruhe, Germany.; Department of Chemistry, Bielefeld University, Postfach 100131, 33501 Bielefeld, Germany.; Pediatric Infectious Diseases, University Children's Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. |
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Abstract: | 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. |
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