title: The pattern-recognition molecule Nod1 is localized at the plasma membrane at sites of bacterial interaction.
abstract: The pattern-recognition molecule Nod1 is a critical sensor for bacterial derived diaminopimelic acid-containing peptidoglycan fragments which induces innate immune responses in epithelial cells. Here we report the subcellular localization of this protein in human epithelial cells. Nod1 is localized in the cytosol and at the plasma membrane in human cells. This membrane association is dependent on the integrity of the protein, on its signalling capacity and on an intact actin cytoskeleton. Signalling-inactive mutants of Nod1 or disruption of the actin cytoskeleton interferes with this localization pattern and impacts on downstream NF-kappaB activation. Moreover, the invasive bacterium Shigella flexneri was used as a model for physiological activation of Nod1. Imaging revealed that Nod1 is recruited to the site of bacterial entry, where it colocalizes with NEMO. Our data provide evidence that membrane association is linked to Nod1 function and, in view of recent findings on Nod2, that this may be a common feature of NLR family members.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, France, and Unité INSERM 786, Institut Pasteur, France. thomas.kufer@uk-koeln.de
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kufer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Adam
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism* / Q000382:microbiology; D003600:Cytosol / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D012763:Shigella flexneri / Q000472:pathogenicity / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D000199:Actins; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein