Article ; Online: Seipin performs dissectible functions in promoting lipid droplet biogenesis and regulating droplet morphology.
2015 Volume 26, Issue 4, Page(s) 726–739
Abstract: Seipin is necessary for both adipogenesis and lipid droplet (LD) organization in nonadipose tissues ... of Saccharomyces cerevisiae include aberrant droplet morphology (endoplasmic reticulum-droplet clusters and size heterogeneity ... in this mutant. We conclude that seipin has dissectible roles in both promoting early LD initiation and ...
| Abstract | Seipin is necessary for both adipogenesis and lipid droplet (LD) organization in nonadipose tissues; however, its molecular function is incompletely understood. Phenotypes in the seipin-null mutant of Saccharomyces cerevisiae include aberrant droplet morphology (endoplasmic reticulum-droplet clusters and size heterogeneity) and sensitivity of droplet size to changes in phospholipid synthesis. It has not been clear, however, whether seipin acts in initiation of droplet synthesis or at a later step. Here we utilize a system of de novo droplet formation to show that the absence of seipin results in a delay in droplet appearance with concomitant accumulation of neutral lipid in membranes. We also demonstrate that seipin is required for vectorial budding of droplets toward the cytoplasm. Furthermore, we find that the normal rate of droplet initiation depends on 14 amino acids at the amino terminus of seipin, deletion of which results in fewer, larger droplets that are consistent with a delay in initiation but are otherwise normal in morphology. Importantly, other functions of seipin, namely vectorial budding and resistance to inositol, are retained in this mutant. We conclude that seipin has dissectible roles in both promoting early LD initiation and in regulating LD morphology, supporting its importance in LD biogenesis. |
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| MeSH term(s) | Cytoplasm/metabolism ; Cytoplasm/ultrastructure ; Endoplasmic Reticulum/metabolism ; GTP-Binding Protein gamma Subunits/genetics ; GTP-Binding Protein gamma Subunits/metabolism ; GTP-Binding Protein gamma Subunits/physiology ; Gene Knockout Techniques ; Lipid Droplets/metabolism ; Lipid Metabolism ; Phenotype ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae/ultrastructure | ||||||||||
| Chemical Substances | GTP-Binding Protein gamma Subunits ; seipin protein, S cerevisiae | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2015-02-15 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 1098979-1 | ||||||||||
| ISSN | 1939-4586 ; 1059-1524 | ||||||||||
| ISSN (online) | 1939-4586 | ||||||||||
| ISSN | 1059-1524 | ||||||||||
| DOI | 10.1091/mbc.E14-08-1303 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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