title: The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1.
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.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: M F Michelle
authors.initials: MF
authors.lastname: Sim
authors.forename: Rowena J
authors.initials: RJ
authors.lastname: Dennis
authors.forename: Evelyne M
authors.initials: EM
authors.lastname: Aubry
authors.forename: Nardev
authors.initials: N
authors.lastname: Ramanathan
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sembongi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saudek
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ito
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Symeon
authors.initials: S
authors.lastname: Siniossoglou
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Rochford
keywords: Adipogenesis; Endoplasmic reticulum; Lipin; Lipodystrophy; Seipin
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