title: Seipin: from human disease to molecular mechanism.
abstract: The most-severe form of congenital generalized lipodystrophy (CGL) is caused by mutations in BSCL2/seipin. Seipin is a homo-oligomeric integral membrane protein in the endoplasmic reticulum that concentrates at junctions with cytoplasmic lipid droplets (LDs). While null mutations in seipin are responsible for lipodystrophy, dominant mutations cause peripheral neuropathy and other nervous system pathologies. We first review the clinical aspects of CGL and the discovery of the responsible genetic loci. The structure of seipin, its normal isoforms, and mutations found in patients are then presented. While the function of seipin is not clear, seipin gene manipulation in yeast, flies, mice, and human cells has recently yielded a trove of information that suggests roles in lipid metabolism and LD assembly and maintenance. A model is presented that attempts to bridge these new data to understand the role of this fascinating protein.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
authors.forename: Bethany R
authors.initials: BR
authors.lastname: Cartwright
authors.forename: Joel M
authors.initials: JM
authors.lastname: Goodman
mesh_terms: D000818:Animals; D004194:Disease / Q000235:genetics; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D052497:Lipodystrophy, Congenital Generalized / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D010641:Phenotype
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits