Open Access Research

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

Gaëlle Blandin12, Sylvie Marchand1, Karine Charton1, Nathalie Danièle1, Evelyne Gicquel1, Jean-Baptiste Boucheteil1, Azéddine Bentaib1, Laetitia Barrault1, Daniel Stockholm1, Marc Bartoli12 and Isabelle Richard1*

Author Affiliations

1 Généthon CNRS UMR8587, 1, rue de l'Internationale, Evry 91000, France

2 Present address: Aix-Marseille Univ and Inserm, UMR 910, Faculté de Médecine Timone, Marseille 13385, France

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Skeletal Muscle 2013, 3:3  doi:10.1186/2044-5040-3-3

Published: 15 February 2013

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.

Keywords:
Interactome; Muscular dystrophies; Yeast-two hybrid