title: Lamellipodin Is Important for Cell-to-Cell Spread and Actin-Based Motility in Listeria monocytogenes.
abstract: Listeria monocytogenes is a foodborne pathogen capable of invading a broad range of cell types and replicating within the host cell cytoplasm. This paper describes the colocalization of host cell lamellipodin (Lpd) with intracellular L. monocytogenes detectable 6 h postinfection of epithelial cells. The association was mediated via interactions between both the peckstrin homology (PH) domain in Lpd and phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] on the bacterial surface and by interactions between the C-terminal EVH1 (Ena/VASP [vasodilator-stimulated phosphoprotein] homology domain 1) binding domains of Lpd and the host VASP (vasodilator-stimulated phosphoprotein) recruited to the bacterial cell surface by the listerial ActA protein. Depletion of Lpd by short interfering RNA (siRNA) resulted in reduced plaque size and number, indicating a role for Lpd in cell-to-cell spread. In contrast, overexpression of Lpd resulted in an increase in the number of L. monocytogenes-containing protrusions (listeriopods). Manipulation of the levels of Lpd within the cell also affected the intracellular velocity of L. monocytogenes, with a reduction in Lpd corresponding to an increase in intracellular velocity. These data, together with the observation that Lpd accumulated at the interface between the bacteria and the developing actin tail at the initiation of actin-based movement, indicate a possible role for Lpd in the actin-based movement and the cell-to-cell spread of L. monocytogenes.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Jane E
authors.initials: JE
authors.lastname: King
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Marie
authors.initials: M
authors.lastname: Goldrick
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Lowe
authors.affiliation: Department of Biology and Center for Cancer Research, MIT, Cambridge, Massachusetts, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom i.s.roberts@manchester.ac.uk.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Roberts
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism / Q000472:pathogenicity*; D008088:Listeriosis / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008565:Membrane Proteins; C493339:RAPH1 protein, human