{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:30:22Z","timestamp":1790764222769,"version":"4.1.0"},"reference-count":37,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The human congenital generalized lipodystrophy type 2 (CGL2) protein seipin\/yeast Fld1 controls lipid droplet (LD) size through an unknown mechanism. Herein, we report that deletion of yeast LDB16\/YCL005W, similar to 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 site, a region that likely links neutral lipid synthesis with LD assembly. The formation of the Fld1-Ldb16 complex involves their putative transmembrane segments, which directly contributes to the maintenance of LD morphology. The stability of Ldb16 requires Fld1, as Ldb16 is subjected to ER-associated degradation (ERAD) without Fld1 but stabilized when Fld1 is present. Strikingly, human seipin but not yeast Fld1 complements the LD defects in ldb16\u0394, implying that seipin covers the function of the Fld1-Ldb16 complex. Together, we propose that human seipin may adopt the architecture of the yeast Fld1-Ldb16 complex for proper size maintenance of LDs.<\/jats:p>","DOI":"10.1242\/jcs.137737","type":"journal-article","created":{"date-parts":[[2014,1,17]],"date-time":"2014-01-17T04:22:42Z","timestamp":1389932562000},"source":"Crossref","is-referenced-by-count":84,"title":["Size control of lipid droplets in budding yeast requires a collaboration of Fld1 and Ldb16"],"prefix":"10.1242","author":[{"given":"Chao-Wen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsuan","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"key":"2021042614253882500_b1","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1126\/science.278.5344.1806","article-title":"Role of Cue1p in ubiquitination and degradation at the ER surface.","volume":"278","author":"Biederer","year":"1997","journal-title":"Science"},{"key":"2021042614253882500_b2","doi-asserted-by":"publisher","first-page":"10747","DOI":"10.1021\/bi1013003","article-title":"Seipin is a discrete homooligomer.","volume":"49","author":"Binns","year":"2010","journal-title":"Biochemistry"},{"key":"2021042614253882500_b3","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.biochi.2009.01.011","article-title":"Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy.","volume":"91","author":"Boutet","year":"2009","journal-title":"Biochimie"},{"key":"2021042614253882500_b4","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1093\/emboj\/21.4.615","article-title":"Role of the ubiquitin-selective CDC48(UFD1\/NPL4 )chaperone (segregase) in ERAD of OLE1 and other substrates.","volume":"21","author":"Braun","year":"2002","journal-title":"EMBO J."},{"key":"2021042614253882500_b5","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1194\/jlr.R023754","article-title":"Seipin: from human disease to molecular mechanism.","volume":"53","author":"Cartwright","year":"2012","journal-title":"J. Lipid Res."},{"key":"2021042614253882500_b6","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.cell.2006.05.043","article-title":"Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins.","volume":"126","author":"Carvalho","year":"2006","journal-title":"Cell"},{"key":"2021042614253882500_b7","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.fgb.2005.05.002","article-title":"A genome-wide screen for Saccharomyces cerevisiae nonessential genes involved in mannosyl phosphate transfer to mannoprotein-linked oligosaccharides.","volume":"42","author":"Corbacho","year":"2005","journal-title":"Fungal Genet. Biol."},{"key":"2021042614253882500_b8","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1093\/hmg\/ddr205","article-title":"Seipin ablation in mice results in severe generalized lipodystrophy.","volume":"20","author":"Cui","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2021042614253882500_b9","doi-asserted-by":"publisher","first-page":"E705","DOI":"10.1152\/ajpendo.00237.2011","article-title":"Overexpression of a short human seipin\/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy.","volume":"302","author":"Cui","year":"2012","journal-title":"Am. J. Physiol."},{"key":"2021042614253882500_b10","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1002\/(SICI)1097-0061(199812)14:16&lt;1471::AID-YEA353&gt;3.0.CO;2-Y","article-title":"Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae.","volume":"14","author":"Daum","year":"1998","journal-title":"Yeast"},{"key":"2021042614253882500_b11","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1128\/EC.00386-07","article-title":"Genome-wide analysis of sterol-lipid storage and trafficking in Saccharomyces cerevisiae.","volume":"7","author":"Fei","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"2021042614253882500_b12","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1083\/jcb.200711136","article-title":"Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast.","volume":"180","author":"Fei","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021042614253882500_b13","doi-asserted-by":"publisher","first-page":"2136","DOI":"10.1194\/jlr.M017566","article-title":"Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis.","volume":"52","author":"Fei","year":"2011","journal-title":"J. Lipid Res."},{"key":"2021042614253882500_b14","doi-asserted-by":"publisher","first-page":"e1002201","DOI":"10.1371\/journal.pgen.1002201","article-title":"A role for phosphatidic acid in the formation of \u201csupersized\u201d lipid droplets.","volume":"7","author":"Fei","year":"2011","journal-title":"PLoS Genet."},{"key":"2021042614253882500_b15","doi-asserted-by":"publisher","first-page":"e00953","DOI":"10.7554\/eLife.00953","article-title":"Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10\/Teb4.","volume":"2","author":"Foresti","year":"2013","journal-title":"Elife"},{"key":"2021042614253882500_b16","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1534\/genetics.111.130286","article-title":"Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae.","volume":"190","author":"Henry","year":"2012","journal-title":"Genetics"},{"key":"2021042614253882500_b17","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/ana.21070","article-title":"Molecular pathogenesis of seipin\/BSCL2-related motor neuron diseases.","volume":"61","author":"Ito","year":"2007","journal-title":"Ann. Neurol."},{"key":"2021042614253882500_b18","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/genetics\/144.4.1425","article-title":"Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast.","volume":"144","author":"James","year":"1996","journal-title":"Genetics"},{"key":"2021042614253882500_b19","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.cmet.2011.07.013","article-title":"Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase.","volume":"14","author":"Krahmer","year":"2011","journal-title":"Cell Metab."},{"key":"2021042614253882500_b20","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1002\/yea.320101105","article-title":"Characterization of lipid particles of the yeast, Saccharomyces cerevisiae.","volume":"10","author":"Leber","year":"1994","journal-title":"Yeast"},{"key":"2021042614253882500_b21","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1002\/(SICI)1097-0061(199807)14:10&lt;953::AID-YEA293&gt;3.0.CO;2-U","article-title":"Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.","volume":"14","author":"Longtine","year":"1998","journal-title":"Yeast"},{"key":"2021042614253882500_b22","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1016\/j.febslet.2006.03.040","article-title":"Membrane topology of the human seipin protein.","volume":"580","author":"Lundin","year":"2006","journal-title":"FEBS Lett."},{"key":"2021042614253882500_b23","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S0022-2836(03)00182-7","article-title":"Reliability measures for membrane protein topology prediction algorithms.","volume":"327","author":"Mel\u00e9n","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2021042614253882500_b24","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.2337\/db08-0184","article-title":"The human lipodystrophy gene BSCL2\/seipin may be essential for normal adipocyte differentiation.","volume":"57","author":"Payne","year":"2008","journal-title":"Diabetes"},{"key":"2021042614253882500_b25","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/S0092-8674(01)00595-5","article-title":"Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1\/NPL4), a ubiquitin-selective chaperone.","volume":"107","author":"Rape","year":"2001","journal-title":"Cell"},{"key":"2021042614253882500_b26","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.molmet.2012.11.002","article-title":"The human lipodystrophy protein seipin is an ER membrane adaptor for the adipogenic PA phosphatase lipin 1.","volume":"2","author":"Sim","year":"2013","journal-title":"Mol. Metab."},{"key":"2021042614253882500_b27","doi-asserted-by":"publisher","first-page":"5433","DOI":"10.1210\/jc.2003-030835","article-title":"Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes.","volume":"88","author":"Simha","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2021042614253882500_b28","doi-asserted-by":"publisher","first-page":"31190","DOI":"10.1074\/jbc.M403251200","article-title":"A yeast strain lacking lipid particles bears a defect in ergosterol formation.","volume":"279","author":"Sorger","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2021042614253882500_b29","doi-asserted-by":"publisher","first-page":"20890","DOI":"10.1073\/pnas.0704154104","article-title":"The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology.","volume":"104","author":"Szymanski","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042614253882500_b30","doi-asserted-by":"publisher","first-page":"e1001364","DOI":"10.1371\/journal.pgen.1001364","article-title":"Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation.","volume":"7","author":"Tian","year":"2011","journal-title":"PLoS Genet."},{"key":"2021042614253882500_b31","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/nrm2546","article-title":"One step at a time: endoplasmic reticulum-associated degradation.","volume":"9","author":"Vembar","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042614253882500_b32","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.bbalip.2008.10.009","article-title":"The life of lipid droplets.","volume":"1791","author":"Walther","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2021042614253882500_b33","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1146\/annurev-biochem-061009-102430","article-title":"Lipid droplets and cellular lipid metabolism.","volume":"81","author":"Walther","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"2021042614253882500_b34","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1242\/jcs.100230","article-title":"The ubiquitin-like (UBX)-domain-containing protein Ubx2\/Ubxd8 regulates lipid droplet homeostasis.","volume":"125","author":"Wang","year":"2012","journal-title":"J. Cell Sci."},{"key":"2021042614253882500_b35","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/0076-6879(92)19015-X","article-title":"Reconstitution of transport from endoplasmic reticulum to Golgi complex using endoplasmic reticulum-enriched membrane fraction from yeast.","volume":"219","author":"Wuestehube","year":"1992","journal-title":"Methods Enzymol."},{"key":"2021042614253882500_b36","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.ceb.2012.05.012","article-title":"Controlling the size of lipid droplets: lipid and protein factors.","volume":"24","author":"Yang","year":"2012","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021042614253882500_b37","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1126\/science.1191026","article-title":"Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism.","volume":"329","author":"Young","year":"2010","journal-title":"Science"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/127\/6\/1214\/1984381\/jcs-127-06-1214.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.137737\/2045892\/jcs137737.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.137737\/2045892\/jcs137737.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T18:23:42Z","timestamp":1621362222000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.137737\/263833\/Size-control-of-lipid-droplets-in-budding-yeast"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,1]]},"references-count":37,"URL":"https:\/\/doi.org\/10.1242\/jcs.137737","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2014,1,1]]},"article-number":"jcs.137737"}}