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Reverse Engineering Gene Network Identifies New Dysferlin-interacting Proteins

Lookup NU author(s): Mafalda Cacciottolo, Dr Steven Laval, Emerita Professor Katherine Bushby

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Abstract

Dysferlin (DYSF) is a type II transmembrane protein implicated in surface membrane repair of muscle. Mutations in dysferlin lead to Limb Girdle Muscular Dystrophy 2B (LGMD2B), Miyoshi Myopathy (MM), and Distal Myopathy with Anterior Tibialis onset (DMAT). The DYSF protein complex is not well understood, and only a few protein-binding partners have been identified thus far. To increase the set of interacting protein partners for DYSF we recovered a list of predicted interacting protein through a systems biology approach. The predictions are part of a "reverse-engineered" genome-wide human gene regulatory network obtained from experimental data by computational analysis. The reverse-engineering algorithm behind the analysis relates genes to each other based on changes in their expression patterns. DYSF and AHNAK were used to query the system and extract lists of potential interacting proteins. Among the 32 predictions the two genes share, we validated the physical interaction between DYSF protein with moesin (MSN) and polymerase I and transcript release factor (PTRF) in mouse heart lysate, thus identifying two novel Dysferlin-interacting proteins. Our strategy could be useful to clarify Dysferlin function in intracellular vesicles and its implication in muscle membrane resealing.


Publication metadata

Author(s): Cacciottolo M, Belcastro V, Laval S, Bushby K, di Bernardo D, Nigro V

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2011

Volume: 286

Issue: 7

Pages: 5404-5413

Print publication date: 18/02/2011

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology

URL: http://dx.doi.org/10.1074/jbc.M110.173559

DOI: 10.1074/jbc.M110.173559


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Funding

Funder referenceFunder name
Telethon-UILDM
(Ricerca Finalizzata RF-MUL-2007-666195)Ministero della Salute
(TIGEM-TNP42TELC)Telethon
223143Telethon
FP7/2007-2013Telethon

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