Szymanski KM~Goodman JM, 2007

Pubmed ID 18093937
Title The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology.
Authors Kimberly M Szymanski, Derk Binns, René Bartz, Nick V Grishin, Wei-Ping Li, Anil K Agarwal, Abhimanyu Garg, Richard G W Anderson, Joel M Goodman
Abstract Lipodystrophy is a disorder characterized by a loss of adipose tissue often accompanied by severe hypertriglyceridemia, insulin resistance, diabetes, and fatty liver. It can be inherited or acquired. The most severe inherited form is Berardinelli-Seip Congenital Lipodystrophy Type 2, associated with mutations in the BSCL2 gene. BSCL2 encodes seipin, the function of which has been entirely unknown. We now report the identification of yeast BSCL2/seipin through a screen to detect genes important for lipid droplet morphology. The absence of yeast seipin results in irregular lipid droplets often clustered alongside proliferated endoplasmic reticulum (ER); giant lipid droplets are also seen. Many small irregular lipid droplets are also apparent in fibroblasts from a BSCL2 patient. Human seipin can functionally replace yeast seipin, but a missense mutation in human seipin that causes lipodystrophy, or corresponding mutations in the yeast gene, render them unable to complement. Yeast seipin is localized in the ER, where it forms puncta. Almost all lipid droplets appear to be on the ER, and seipin is found at these junctions. Therefore, we hypothesize that seipin is important for droplet maintenance and perhaps assembly. In addition to detecting seipin, the screen identified 58 other genes whose deletions cause aberrant lipid droplets, including 2 genes encoding proteins known to activate lipin, a lipodystrophy locus in mice, and 16 other genes that are involved in endosomal-lysosomal trafficking. The genes identified in our screen should be of value in understanding the pathway of lipid droplet biogenesis and maintenance and the cause of some lipodystrophies.
Citation Proc. Natl. Acad. Sci. U.S.A. 2007; 104:20890-5

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Szymanski KM~Goodman JM, 2007 lipid particle number growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle size growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle size variation growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle aggregation growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle centralization around nuclear envelope growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle staining intensity growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle resolution growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle ring shape growth phase [log] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle number growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle size growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle size variation growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle aggregation growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle centralization around nuclear envelope growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle staining intensity growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle resolution growth phase [stationary] hap alpha ~4,936 Discrete
Szymanski KM~Goodman JM, 2007 lipid particle ring shape growth phase [stationary] hap alpha ~4,936 Discrete

Curation history

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March 27, 2014 To request.
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