Article (Scientific journals)
Modulation of Nod2-dependent NF-kappa B signaling by the actin cytoskeleton
Legrand, Sylvie; Kustermans, Gaëlle; Bex, Françoise et al.
2007In Journal of Cell Science, 120 (7), p. 1299-1310
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Keywords :
actin cytoskeleton; NF-kappa B; Nod2; Rac1
Abstract :
[en] Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin disruption induced IKK activation, we studied the human Nod2 protein, which was able to induce NF-kappa B activation and whose expression was restricted to myelomonocytic and intestinal epithelial cells. Nod2 is thought to play key roles in pathogen defence through sensing bacteria and generating an inflammatory immune response. We showed that actin disruption by CytD significantly and specifically increased Nod2-mediated NF-kappa B signaling. Nod2 was fully partitioned in the Triton-X-100-insoluble fraction but translocated into the soluble fraction after CytD treatment, demonstrating that the presence of Nod2 in the detergent-insoluble pellet was specific to actin cytoskeleton. Confocal analysis also revealed a Nod2 colocalization with membrane-associated F-actin. Colocalization and co-immunoprecipitation assays with endogenous Rac1 have shown that Nod2 associated with activated Rac1 in membrane ruffles through both its N-terminal caspase recruitment domains (CARD) and C-terminal leucine-rich repeats (LRRs). Membrane ruffle disruption by a Rac1 dominant negative form primed Nod2-dependent NF-kappa B signaling. The recruitment of Nod2 in Rac-induced dynamic cytoskeletal structures could be a strategy to both repress the Nod2-dependent NF-kappa B signaling in unstimulated cells and rapidly mobilize Nod2 during bacterial infection.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Legrand, Sylvie ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Kustermans, Gaëlle ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Bex, Françoise;  Université Libre de Bruxelles - ULB > Institute for Microbiological Research J.-M. Wiame > Laboratory of Microbiology
Kufer, Thomas;  Institut Pasteur and INSERM (PARIS, FRANCE) > Unité de Pathogénie Microbienne Moléculaire
Kremmer, Elisabeth;  GSF-Institut für Molekulare Immunologie (Germany)
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie
Language :
English
Title :
Modulation of Nod2-dependent NF-kappa B signaling by the actin cytoskeleton
Publication date :
01 April 2007
Journal title :
Journal of Cell Science
ISSN :
0021-9533
eISSN :
1477-9137
Publisher :
Company Of Biologists, Cambridge, United Kingdom
Volume :
120
Issue :
7
Pages :
1299-1310
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 24 March 2009

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