A role for alpha-and beta-catenins in bacterial uptake.
Interaction of internalin with E-cadherin promotes entry of Listeria monocytogenes into human epithelial cells. This process requires actin cytoskeleton rearrangements. Here we show, by using a series of stably transfected cell lines expressing E-cadherin variants, that the ectodomain of E-cadherin is sufficient for bacterial adherence and that the intracytoplasmic domain is required for entry. The critical cytoplasmic region was further mapped to the beta-catenin binding domain. Because beta-catenin is known to interact with alpha-catenin, which binds to actin, we generated a fusion molecule consisting of the ectodomain of E-cadherin and the actin binding site of alpha-catenin. Cells expressing this chimera were as permissive as E-cadherin-expressing cells. In agreement with these data, alpha- and beta-catenins as well as E-cadherin clustered and colocalized at the entry site, where F-actin then accumulated. Taken together, these results reveal that E-cadherin, via beta- and alpha-catenins, can trigger dynamic events of actin polymerization and membrane extensions culminating in bacterial uptake.
Lecuit
M
M
Unité des Interactions Bactéries-Cellules, Station Centrale de Microscopie Electronique, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Hurme
R
R
Pizarro-Cerda
J
J
Ohayon
H
H
Geiger
B
B
Cossart
P
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006801:Humans; D008087:Listeria / Q000502:physiology* / Q000648:ultrastructure; D008089:Listeria monocytogenes / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin
D000199:Actins; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin