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FHL1B Interacts with lamin A/C and emerin at the nuclear lamina and is misregulated in Emery-Dreifuss Muscular Dystrophy

Item Type:Article
Title:FHL1B Interacts with lamin A/C and emerin at the nuclear lamina and is misregulated in Emery-Dreifuss Muscular Dystrophy
Creators Name:Ziat, E. and Mamchaoui, K. and Beuvin, M. and Nelson, I. and Azibani, F. and Spuler, S. and Bonne, G. and Bertrand, A.T.
Abstract:BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) is associated with mutations in EMD and LMNA genes, encoding for the nuclear envelope proteins emerin and lamin A/C, indicating that EDMD is a nuclear envelope disease. We recently reported mutations in FHL1 gene in X-linked EDMD. FHL1 encodes FHL1A, and the two minor isoforms FHL1B and FHL1C. So far, none have been described at the nuclear envelope. OBJECTIVE: To gain insight into the pathophysiology of EDMD, we focused our attention on the poorly characterized FHL1B isoform. METHODS: The amount and the localisation of FHL1B were evaluated in control and diseased human primary myoblasts using immunofluorescence and western blotting. RESULTS: We found that in addition to a cytoplasmic localization, this isoform strongly accumulated at the nuclear envelope of primary human myoblasts, like but independently of lamin A/C and emerin. During myoblast differentiation, we observed a major reduction of FHL1B protein expression, especially in the nucleus. Interestingly, we found elevated FHL1B expression level in myoblasts from an FHL1-related EDMD patient where the FHL1 mutation only affects FHL1A, as well as in myoblasts from an LMNA-related EDMD patient. CONCLUSIONS: Altogether, the specific localization of FHL1B and its modulation in disease-patient's myoblasts confirmed FHL1-related EDMD as a nuclear envelope disease.
Keywords:FHL1B, Emerin, Lamin A/C, Nuclear Envelope, Emery-Dreifuss Muscular Dystrophy
Source:Journal of Neuromuscular Diseases
ISSN:2214-3599
Publisher:IOS Press (Netherlands)
Volume:3
Number:4
Page Range:497-510
Date:29 November 2016
Official Publication:https://doi.org/10.3233/JND-160169
PubMed:View item in PubMed

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