TY - JOUR
T1 - The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1
AU - Sim, M. F.Michelle
AU - Dennis, Rowena J.
AU - Aubry, Evelyne M.
AU - Ramanathan, Nardev
AU - Sembongi, Hiroshi
AU - Saudek, Vladimir
AU - Ito, Daisuke
AU - O'Rahilly, Stephen
AU - Siniossoglou, Symeon
AU - Rochford, Justin J.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Adipogenesis
KW - Endoplasmic reticulum
KW - Lipin
KW - Lipodystrophy
KW - Seipin
UR - http://www.scopus.com/inward/record.url?scp=84885850160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885850160&partnerID=8YFLogxK
U2 - 10.1016/j.molmet.2012.11.002
DO - 10.1016/j.molmet.2012.11.002
M3 - Article
AN - SCOPUS:84885850160
VL - 2
SP - 38
EP - 46
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
IS - 1
ER -