title: Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast.
abstract: Lipid droplets (LDs) are emerging cellular organelles that are of crucial importance in cell biology and human diseases. In this study, we present our screen of approximately 4,700 Saccharomyces cerevisiae mutants for abnormalities in the number and morphology of LDs; we identify 17 fld (few LDs) and 116 mld (many LDs) mutants. One of the fld mutants (fld1) is caused by the deletion of YLR404W, a previously uncharacterized open reading frame. Cells lacking FLD1 contain strikingly enlarged (supersized) LDs, and LDs from fld1Delta cells demonstrate significantly enhanced fusion activities both in vivo and in vitro. Interestingly, the expression of human seipin, whose mutant forms are associated with Berardinelli-Seip congenital lipodystrophy and motoneuron disorders, rescues LD-associated defects in fld1Delta cells. Lipid profiling reveals alterations in acyl chain compositions of major phospholipids in fld1Delta cells. These results suggest that an evolutionally conserved function of seipin in phospholipid metabolism and LD formation may be functionally important in human adipogenesis.
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore 117597, Republic of Singapore.
authors.forename: Weihua
authors.initials: W
authors.lastname: Fei
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Bruno
authors.initials: B
authors.lastname: Gaeta
authors.forename: Ximing
authors.initials: X
authors.lastname: Du
authors.forename: Lars
authors.initials: L
authors.lastname: Kuerschner
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D015388:Organelles / Q000378:metabolism* / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: C432679:BSCL2 protein, human; C527368:Fld1 protein, S cerevisiae; D044388:GTP-Binding Protein gamma Subunits; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins