CD44-independent activation of the Met signaling pathway by HGF and InlB.
Listeria monocytogenes is a facultative intracellular Gram-positive bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The L. monocytogenes surface protein InlB interacts with c-Met, the hepatocyte growth factor (HGF) receptor, inducing bacterial internalization in numerous non-phagocytic cells. As InlB and HGF are known to trigger similar signaling pathways upon c-Met activation, we investigated the role of CD44, and more specifically its isoform CD44v6, in bacterial internalization in non-phagocytic cells. Indeed, CD44, the hyaluronic acid transmembrane receptor, and more specifically its isoform CD44v6 have been reported as necessary for the activation of c-Met upon the interaction with either the endogenous ligand HGF or the L. monocytogenes surface protein InlB. Our results demonstrate that, in the cell lines that we used, CD44 receptors play no role in the activation of c-Met, neither during L. monocytogenes entry, nor upon HGF activation. Furthermore, none of the CD44 isoforms was recruited at the L. monocytogenes entry site, and depletion by siRNA of total CD44 or of CD44v6 isoform did not reduce bacterial infections. Conversely, the overexpression of CD44 or CD44v6 had no significant effect on L. monocytogenes internalization. Together our results reveal that the activation of c-Met can be largely CD44-independent.
Dortet
Laurent
L
Institut Pasteur, Unité des interactions Bactéries-Cellules, 25 rue du Dr. Roux, 75015 Paris, France.
Veiga
Esteban
E
Bonazzi
Matteo
M
Cossart
Pascale
P
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D020868:Gene Silencing; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D001426:Bacterial Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C095768:inlB protein, Listeria monocytogenes; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met