title: Control of lipid droplet size in budding yeast requires the collaboration between Fld1 and Ldb16.
abstract: The human congenital generalized lipodystrophy type 2 protein seipin (Fld1 in budding yeast) controls lipid droplet (LD) size through an unknown mechanism. Here, we report that deletion of yeast LDB16/YCL005W, similar to deletion of FLD1, causes supersized and small clustered LDs, altered phospholipid metabolism and impaired distribution of a subset of LD proteins. Ldb16 is a transmembrane protein in the endoplasmic reticulum (ER) that assembles together with Fld1 at ER-LD contact sites, a region that probably links neutral lipid synthesis with LD assembly. The formation of the Fld1-Ldb16 complex involves putative transmembrane segments of both proteins, thus, directly contributing to the maintenance of LD morphology. The stability of Ldb16 requires Fld1, as Ldb16 is subjected to ER-associated degradation (ERAD) in the absence of Fld1 but is stabilized when Fld1 is present. Strikingly, human seipin, but not yeast Fld1, complements the defects in LDs in ldb16Δ yeast, implying that seipin can substitute for the function of the Fld1-Ldb16 complex. We propose that human seipin might adopt the architecture of the yeast Fld1-Ldb16 complex in order to properly maintain the size of LDs.
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan.
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Wang
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Miao
authors.forename: Yi-Shun
authors.initials: YS
authors.lastname: Chang
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D044388:GTP-Binding Protein gamma Subunits / Q000096:biosynthesis; D055786:Gene Knockout Techniques; D006801:Humans; D066292:Lipid Droplets / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D053141:Organelle Size; D055550:Protein Stability; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C432679:BSCL2 protein, human; C527368:Fld1 protein, S cerevisiae; D044388:GTP-Binding Protein gamma Subunits; C000594798:LDB16 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: ER-associated degradation; Endoplasmic reticulum; Fld1; Ldb16; Lipid droplets; Seipin