A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Skeletal Muscle Year : 2013

A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.

Gaëlle Blandin
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Sylvie Marchand
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Karine Charton
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Nathalie Danièle
Evelyne Gicquel
Jean-Baptiste Boucheteil
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Azéddine Bentaib
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Laetitia Barrault
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Daniel Stockholm
Marc Bartoli
Isabelle Richard
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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/gamma-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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Dates and versions

inserm-00805816 , version 1 (29-03-2013)

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Gaëlle Blandin, Sylvie Marchand, Karine Charton, Nathalie Danièle, Evelyne Gicquel, et al.. A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome.. Skeletal Muscle, 2013, 3 (1), pp.3. ⟨10.1186/2044-5040-3-3⟩. ⟨inserm-00805816⟩

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