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FHL1B Interacts with Lamin A/C and Emerin at the Nuclear Lamina and is Misregulated in Emery-Dreifuss Muscular Dystrophy.
J Neuromuscul Dis. 2016 11 29; 3(4):497-510.JN

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.

Authors+Show Affiliations

Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France. Muscle Research Unit, Experimental and Clinical Research Center, A Joint Cooperation between Max-Delbrück-Center for Molecular Medicine and Charite Medical Faculty, Berlin, Germany.Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.Muscle Research Unit, Experimental and Clinical Research Center, A Joint Cooperation between Max-Delbrück-Center for Molecular Medicine and Charite Medical Faculty, Berlin, Germany.Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center of Research in Myology, F-75013 Paris, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27911330

Citation

Ziat, Esma, et al. "FHL1B Interacts With Lamin A/C and Emerin at the Nuclear Lamina and Is Misregulated in Emery-Dreifuss Muscular Dystrophy." Journal of Neuromuscular Diseases, vol. 3, no. 4, 2016, pp. 497-510.
Ziat E, Mamchaoui K, Beuvin M, et al. FHL1B Interacts with Lamin A/C and Emerin at the Nuclear Lamina and is Misregulated in Emery-Dreifuss Muscular Dystrophy. J Neuromuscul Dis. 2016;3(4):497-510.
Ziat, E., Mamchaoui, K., Beuvin, M., Nelson, I., Azibani, F., Spuler, S., Bonne, G., & Bertrand, A. T. (2016). FHL1B Interacts with Lamin A/C and Emerin at the Nuclear Lamina and is Misregulated in Emery-Dreifuss Muscular Dystrophy. Journal of Neuromuscular Diseases, 3(4), 497-510.
Ziat E, et al. FHL1B Interacts With Lamin A/C and Emerin at the Nuclear Lamina and Is Misregulated in Emery-Dreifuss Muscular Dystrophy. J Neuromuscul Dis. 2016 11 29;3(4):497-510. PubMed PMID: 27911330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FHL1B Interacts with Lamin A/C and Emerin at the Nuclear Lamina and is Misregulated in Emery-Dreifuss Muscular Dystrophy. AU - Ziat,Esma, AU - Mamchaoui,Kamel, AU - Beuvin,Maud, AU - Nelson,Isabelle, AU - Azibani,Feriel, AU - Spuler,Simone, AU - Bonne,Gisèle, AU - Bertrand,Anne T, PY - 2016/12/3/entrez PY - 2016/12/3/pubmed PY - 2018/3/16/medline KW - Emery-Dreifuss muscular dystrophy KW - FHL1B KW - emerin KW - lamin A/C KW - nuclear envelope SP - 497 EP - 510 JF - Journal of neuromuscular diseases JO - J Neuromuscul Dis VL - 3 IS - 4 N2 - 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. SN - 2214-3599 UR - https://www.unboundmedicine.com/medline/citation/27911330/FHL1B_Interacts_with_Lamin_A/C_and_Emerin_at_the_Nuclear_Lamina_and_is_Misregulated_in_Emery_Dreifuss_Muscular_Dystrophy_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JND-160169 DB - PRIME DP - Unbound Medicine ER -