title: Site specific cleavage mediated by MMPs regulates function of agrin.
abstract: BACKGROUND
  Agrin is the key inducer of postsynaptic differentiations at the neuromuscular junction. The multidomain heparan sulfate proteoglycan is mediating via its N-terminal segment the interaction with laminin, whereas the C-terminal portion is responsible for Dystroglycan binding and clustering of the Acetylcholine receptor. Matrix metalloproteinases (MMP) are known to play essential roles in matrix remodeling, degradation and regulation of extracellular signaling networks.
  
  
  RESULTS
  Site-specific processing of Agrin provides key insight into regulatory effects of Matrix metalloproteinases (MMPs). Here, we present a detailed study of agrin processing by different MMPs together with a molecular understanding of binding and cleavage at both terminal fragments. The data suggest for a regulatory effect of MMP cleavage at particularly important functional sites of agrin. Cleave of agrin abolishes the agrin-laminin complex formation and the Acetylcholine receptor clustering at the neuromuscular junction.
  
  
  CONCLUSIONS
  Agrin is a target of specific MMP processing resulting in agrin subfragments with different regulatory activities. MMP processing is a powerful tool to regulate extracellular signaling networks.
authors.affiliation: Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Trushar R
authors.initials: TR
authors.lastname: Patel
authors.forename: Georgina
authors.initials: G
authors.lastname: Butler
authors.forename: Ainsley
authors.initials: A
authors.lastname: McFarlane
authors.forename: Irene
authors.initials: I
authors.lastname: Xie
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Overall
authors.forename: Jörg
authors.initials: J
authors.lastname: Stetefeld
mesh_terms: D018171:Agrin / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D018171:Agrin; D007797:Laminin; D020782:Matrix Metalloproteinases