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

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.


  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.

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Correspondence to Brigitte Buendia.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Buendia, B. LMNA p.R482W mutation related to FPLD2 alters SREBP1-A type lamin interactions in human fibroblasts and adipose stem cells. Orphanet J Rare Dis 10 (Suppl 2), O13 (2015).

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