title: A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.
abstract: BACKGROUND
  The complexity of the skeletal muscle and the identification of numerous human disease-causing mutations in its constitutive proteins make it an interesting tissue for proteomic studies aimed at understanding functional relationships of interacting proteins in both health and diseases.
  
  
  METHODS
  We undertook a large-scale study using two-hybrid screens and a human skeletal-muscle cDNA library to establish a proteome-scale map of protein-protein interactions centered on proteins involved in limb-girdle muscular dystrophies (LGMD). LGMD is a group of more than 20 different neuromuscular disorders that principally affect the proximal pelvic and shoulder girdle muscles.
  
  
  CONCLUSIONS
  The interaction network we unraveled incorporates 1018 proteins connected by 1492 direct binary interactions and includes 1420 novel protein-protein interactions. Computational, experimental and literature-based analyses were performed to assess the overall quality of this network. Interestingly, LGMD proteins were shown to be highly interconnected, in particular indirectly through sarcomeric proteins. In-depth mining of the LGMD-centered interactome identified new candidate genes for orphan LGMDs and other neuromuscular disorders. The data also suggest the existence of functional links between LGMD2B/dysferlin and gene regulation, between LGMD2C/γ-sarcoglycan and energy control and between LGMD2G/telethonin and maintenance of genome integrity. This dataset represents a valuable resource for future functional investigations.
authors: Généthon CNRS UMR8587, 1, rue de l'Internationale, Evry 91000, France. richard@genethon.fr.
authors: Gaëlle
authors: G
authors: Blandin
authors: Sylvie
authors: S
authors: Marchand
authors: Karine
authors: K
authors: Charton
authors: Nathalie
authors: N
authors: Danièle
authors: Evelyne
authors: E
authors: Gicquel
authors: Jean-Baptiste
authors: JB
authors: Boucheteil
authors: Azéddine
authors: A
authors: Bentaib
authors: Laetitia
authors: L
authors: Barrault
authors: Daniel
authors: D
authors: Stockholm
authors: Marc
authors: M
authors: Bartoli
authors: Isabelle
authors: I
authors: Richard