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  • Oral presentation
  • Open Access

LMNA p.R482W mutation related to FPLD2 alters SREBP1-A type lamin interactions in human fibroblasts and adipose stem cells

Orphanet Journal of Rare Diseases201510(Suppl 2):O13

https://doi.org/10.1186/1750-1172-10-S2-O13

Published: 11 November 2015

Keywords

  • Lipodystrophy
  • Adipogenic Differentiation
  • Nuclear Periphery
  • Sterol Regulatory Element Binding Protein
  • R482W Mutation

SREBP1 (Sterol regulatory element binding protein 1), transcription factor that regulates hundreds of genes involved in lipid metabolism and adipocyte differentiation, is a direct partner of A-type lamins. We show that i) in vitro, the tail regions of prelamin A, lamin A and lamin C bind a polypeptide of SREBP1 and ii) within cells, interactions between wild-type A-type lamins and SREBP1 occur mainly at the nuclear periphery but also within the nucleoplasm. While A-type lamin R482W mutation is responsible for Dunnigan type familial partial lipodystrophy (FPLD2), we show that both overexpression of LMNA p.R482W in primary human preadipocytes and endogenous expression of A-type lamins p.R482W in FPLD2 patient fibroblasts, reduce A-type lamins-SREBP1 in situ interactions and upregulates a large number of SREBP1 target genes[1]. As this LMNA mutant was previously shown to inhibit adipogenic differentiation, we propose that deregulation of SREBP1 by mutated A-type lamins constitutes one underlying mechanism of the physiopathology of FPLD2.

Authors’ Affiliations

(1)
Unité de Biologie Fonctionnelle et Adaptative (BFA), Université Paris Diderot-Paris 7, CNRS, Paris, France

References

  1. Vadrot N, Duband-Goulet I, Cabet E, Attanda W, Barateau A, Vicart P, et al: The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy. Human molecular genetics. 2015, 24 (7): 2096-109.PubMedView ArticleGoogle Scholar

Copyright

© Buendia 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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