Journal of Molecular Medicine

, Volume 86, Issue 4, pp 423–432 | Cite as

The Crohn’s disease susceptibility gene DLG5 as a member of the CARD interaction network

  • Frauke Friedrichs
  • Liesbet Henckaerts
  • Severine Vermeire
  • Torsten Kucharzik
  • Tanja Seehafer
  • Maren Möller-Krull
  • Erich Bornberg-Bauer
  • Monika Stoll
  • January Weiner3rd
Original Article

Abstract

Discs large homolog 5 (DLG5), a member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, has been associated with Crohn’s disease (CD), but its role in the pathogenesis of this inflammatory bowel disease is disputed. Here, we used sequence comparisons and phylogenies to analyse the DLG5 gene and its protein product. We identified a 5′ exon, which codes for an N-terminal caspase recruitment domain (CARD) and experimentally confirmed its expression in colonic tissue. DLG5 shares this new domain with nucleotide-binding oligomerisation domain containing 2 (NOD2); the first CD susceptibility factor identified in genetic studies. An extensive phylogenetic analysis redefines the family organisation of the MAGUK proteins: DLG5 is closely related to CARD10, CARD11 and CARD14, CARD-containing proteins which initiate pro-inflammatory NFκB signalling, but not to DLG1–4, previously considered the closest related proteins. Therefore, we suggest renaming DLG5 to correctly annotate the gene in its phylogenetic and functional context. Our study provides evidence that the scaffolding protein DLG5 belongs to the CARD protein family. Thus, DLG5 likely acts in the regulation of NFkB activation or caspase activation as part of host defence mechanisms. As there is substantial crosstalk between CARD-mediated pathways, both CD susceptibility genes, NOD2 and DLG5, may interact functionally to contribute to CD risk.

Keywords

DLG5 Crohn’s disease Caspase recruitment domain 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Frauke Friedrichs
    • 1
  • Liesbet Henckaerts
    • 2
  • Severine Vermeire
    • 2
  • Torsten Kucharzik
    • 3
  • Tanja Seehafer
    • 1
  • Maren Möller-Krull
    • 4
  • Erich Bornberg-Bauer
    • 5
  • Monika Stoll
    • 1
  • January Weiner3rd
    • 5
  1. 1.Department of Genetic Epidemiology, Leibniz-Institute for Arteriosclerosis ResearchUniversity MünsterMünsterGermany
  2. 2.Department of GastroenterologyUniversity Hospital GasthuisbergLeuvenBelgium
  3. 3.Department of Medicine BUniversity of MünsterMünsterGermany
  4. 4.Institute of Experimental Pathology (ZMBE)University of MünsterMünsterGermany
  5. 5.Division of Bioinformatics, Institute for Evolution and BiodiversityUniversity of MünsterMünsterGermany

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