title: The Chlamydia pneumoniae invasin protein Pmp21 recruits the EGF receptor for host cell entry.
abstract: Infection of mammalian cells by the strictly intracellular pathogens Chlamydiae requires adhesion and internalization of the infectious Elementary Bodies (EBs). The components of the latter step were unknown. Here, we identify Chlamydia pneumoniae Pmp21 as an invasin and EGFR as its receptor. Modulation of EGFR surface expression evokes correlated changes in EB adhesion, internalization and infectivity. Ectopic expression of EGFR in EGFR-negative hamster cells leads to binding of Pmp21 beads and EBs, thus boosting the infection. EB/Pmp21 binding and invasion of epithelial cells results in activation of EGFR, recruitment of adaptors Grb2 and c-Cbl and activation of ERK1/2, while inhibition of EGFR or MEK kinase activity abrogates EB entry, but not attachment. Binding of Grb2 and c-Cbl by EGFR is essential for infection. This is the first report of an invasin-receptor interaction involved in host-cell invasion by any chlamydial species.
authors: Funktionelle Genomforschung der Mikroorganismen, Heinrich-Heine Universität, Düsseldorf, Germany.
authors: Katja
authors: K
authors: Mölleken
authors: Elisabeth
authors: E
authors: Becker
authors: Johannes H
authors: JH
authors: Hegemann
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D023521:Chlamydophila Infections / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000378:metabolism / Q000472:pathogenicity*; D006224:Cricetinae; D003412:Cricetulus; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D008863:Microspheres; D011485:Protein Binding; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D001425:Bacterial Outer Membrane Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C484024:polymorphic membrane protein 21, Chlamydophila pneumoniae; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C067419:CBL protein, human
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