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. METHOD: 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. RESULTS AND CONCLUSION: 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.
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Authors | Gaëlle Blandin, Sylvie Marchand, Karine Charton, Nathalie Danièle, Evelyne Gicquel, Jean-Baptiste Boucheteil, Azéddine Bentaib, Laetitia Barrault, Daniel Stockholm, Marc Bartoli, Isabelle Richard |
Journal | Skeletal muscle
(Skelet Muscle)
Vol. 3
Issue 1
Pg. 3
(Feb 15 2013)
ISSN: 2044-5040 [Print] England |
PMID | 23414517
(Publication Type: Journal Article)
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