The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1

M. F.Michelle Sim, Rowena J. Dennis, Evelyne M. Aubry, Nardev Ramanathan, Hiroshi Sembongi, Vladimir Saudek, Daisuke Ito, Stephen O'Rahilly, Symeon Siniossoglou, Justin J. Rochford

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Disruption of the gene BSCL2 causes a severe, generalised lipodystrophy, demonstrating the critical role of its protein product, seipin, in human adipose tissue development. Seipin is essential for adipocyte differentiation, whilst the study of seipin in non-adipose cells has suggested a role in lipid droplet formation. However, its precise molecular function remains poorly understood. Here we demonstrate that seipin can inducibly bind lipin 1, a phosphatidic acid (PA) phosphatase important for lipid synthesis and adipogenesis. Knockdown of seipin during early adipogenesis decreases the association of lipin 1 with membranes and increases the accumulation of its substrate PA. Conversely, PA levels are reduced in differentiating cells by overexpression of wild-type seipin but not by expression of a mutated seipin that is unable to bind lipin 1. Together our data identify lipin as the first example of a seipin-interacting protein and reveals a novel molecular function for seipin in developing adipocytes.

Original languageEnglish
Pages (from-to)38-46
Number of pages9
JournalMolecular Metabolism
Volume2
Issue number1
DOIs
Publication statusPublished - 2013 Feb

Keywords

  • Adipogenesis
  • Endoplasmic reticulum
  • Lipin
  • Lipodystrophy
  • Seipin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1'. Together they form a unique fingerprint.

  • Cite this

    Sim, M. F. M., Dennis, R. J., Aubry, E. M., Ramanathan, N., Sembongi, H., Saudek, V., Ito, D., O'Rahilly, S., Siniossoglou, S., & Rochford, J. J. (2013). The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1. Molecular Metabolism, 2(1), 38-46. https://doi.org/10.1016/j.molmet.2012.11.002