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PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection.

  • McEwan DG Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.
  • Richter B Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.
  • Claudi B Infection Biology, Biozentrum, University Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
  • Wigge C Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Str. 15, Goethe University 60438 Frankfurt am Main, Germany.
  • Wild P Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.
  • Farhan H Infection Biology, Biozentrum, University Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland; Biotechnology Institute Thurga, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
  • McGourty K Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
  • Coxon FP Musculoskeletal Research Programme, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
  • Franz-Wachtel M Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
  • Perdu B Department of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43B, 2650 Edegem, Belgium.
  • Akutsu M Infection Biology, Biozentrum, University Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
  • Habermann A Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Str. 15, Goethe University 60438 Frankfurt am Main, Germany.
  • Kirchof A Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.
  • Helfrich MH Musculoskeletal Research Programme, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
  • Odgren PR Deptartment of Cell Biology, S7-242, University of Massachusetts Medical School, North Worcester, MA 01655, USA.
  • Van Hul W Department of Medical Genetics, University of Antwerp, Prins Boudewijnlaan 43B, 2650 Edegem, Belgium.
  • Frangakis AS Infection Biology, Biozentrum, University Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland.
  • Rajalingam K Molecular Signaling Unit, FZI, Institute for immunology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, Mainz 55131, Germany.
  • Macek B Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany.
  • Holden DW Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
  • Bumann D Infection Biology, Biozentrum, University Basel, Klingelbergstr. 50/70, CH-4056 Basel, Switzerland. Electronic address: dirk.bumann@unibas.ch.
  • Dikic I Institute of Biochemistry II, Goethe University School of Medicine, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany; Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Str. 15, Goethe University 60438 Frankfurt am Main, Germany; University of Split, School of Medicine, Department of Immunology and Medical Genetics, Soltanska 2, 21 000 Split, Croatia. Electronic address: Ivan.Dikic@biochem2.de.
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  • 2014-12-16
Published in:
  • Cell host & microbe. - 2015
Adaptor Proteins, Signal Transducing
Animals
Bacterial Proteins
Carrier Proteins
Glycoproteins
Host-Pathogen Interactions
Humans
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Nuclear Proteins
Protein Binding
Protein Interaction Mapping
Salmonella typhimurium
Vacuoles
rab GTP-Binding Proteins
English The host endolysosomal compartment is often manipulated by intracellular bacterial pathogens. Salmonella (Salmonella enterica serovar Typhimurium) secrete numerous effector proteins, including SifA, through a specialized type III secretion system to hijack the host endosomal system and generate the Salmonella-containing vacuole (SCV). To form this replicative niche, Salmonella targets the Rab7 GTPase to recruit host membranes through largely unknown mechanisms. We show that Pleckstrin homology domain-containing protein family member 1 (PLEKHM1), a lysosomal adaptor, is targeted by Salmonella through direct interaction with SifA. By binding the PLEKHM1 PH2 domain, Salmonella utilize a complex containing PLEKHM1, Rab7, and the HOPS tethering complex to mobilize phagolysosomal membranes to the SCV. Depletion of PLEKHM1 causes a profound defect in SCV morphology with multiple bacteria accumulating in enlarged structures and significantly dampens Salmonella proliferation in multiple cell types and mice. Thus, PLEKHM1 provides a critical interface between pathogenic infection and the host endolysosomal system.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/270589
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