{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:15:23Z","timestamp":1791983723036,"version":"4.4.0"},"reference-count":131,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH RO1GM098583"],"award-info":[{"award-number":["NIH RO1GM098583"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Fat stored in the form of lipid droplets has long been considered a defining characteristic of cytoplasm. However, recent studies have shown that nuclear lipid droplets occur in multiple cells and tissues, including in human patients with fatty liver disease. The function(s) of stored fat in the nucleus has not been determined, and it is possible that nuclear fat is beneficial in some situations. Conversely, nuclear lipid droplets might instead be deleterious by disrupting nuclear organization or triggering aggregation of hydrophobic proteins. We show here that nuclear lipid droplets occur normally in <jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic> intestinal cells and germ cells, but appear to be associated with damage only in the intestine. Lipid droplets in intestinal nuclei can be associated with novel bundles of microfilaments (nuclear actin) and membrane tubules that might have roles in damage repair. To increase the normal, low frequency of nuclear lipid droplets in wild-type animals, we used a forward genetic screen to isolate mutants with abnormally large or abundant nuclear lipid droplets. Genetic analysis and cloning of three such mutants showed that the genes encode the lipid regulator SEIP-1\/seipin, the inner nuclear membrane protein NEMP-1\/Nemp1\/TMEM194A, and a component of COPI vesicles called COPA-1\/\u03b1-COP. We present several lines of evidence that the nuclear lipid droplet phenotype of <jats:italic>copa-1<\/jats:italic> mutants results from a defect in retrieving mislocalized membrane proteins that normally reside in the endoplasmic reticulum. The <jats:italic>seip-1<\/jats:italic> mutant causes most germ cells to have nuclear lipid droplets, the largest of which occupy more than a third of the nuclear volume. Nevertheless, the nuclear lipid droplets do not trigger apoptosis, and the germ cells differentiate into gametes that produce viable, healthy progeny. Thus, our results suggest that nuclear lipid droplets are detrimental to intestinal nuclei, but have no obvious deleterious effect on germ nuclei.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009602","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T17:24:55Z","timestamp":1623864295000},"page":"e1009602","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Nuclear lipid droplets and nuclear damage in Caenorhabditis elegans"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-2250","authenticated-orcid":true,"given":"Jose Verdezoto","family":"Mosquera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3264-5028","authenticated-orcid":true,"given":"Meghan C.","family":"Bacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4087-7419","authenticated-orcid":true,"given":"James R.","family":"Priess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"issue":"11","key":"pgen.1009602.ref001","doi-asserted-by":"crossref","first-page":"R470","DOI":"10.1016\/j.cub.2015.04.004","article-title":"Expanding roles for lipid droplets","volume":"25","author":"MA Welte","year":"2015","journal-title":"Curr Biol"},{"issue":"12","key":"pgen.1009602.ref002","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201898947","article-title":"The assembly of lipid droplets and their roles in challenged cells","volume":"37","author":"WM Henne","year":"2018","journal-title":"EMBO J"},{"issue":"5","key":"pgen.1009602.ref003","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.devcel.2015.11.010","article-title":"Role for Lipid Droplet Biogenesis and Microlipophagy in Adaptation to Lipid Imbalance in Yeast","volume":"35","author":"JD Vevea","year":"2015","journal-title":"Dev Cell"},{"issue":"18","key":"pgen.1009602.ref004","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.cub.2006.07.062","article-title":"The lipid-droplet proteome reveals that droplets are a protein-storage depot","volume":"16","author":"S Cermelli","year":"2006","journal-title":"Curr Biol"},{"issue":"7","key":"pgen.1009602.ref005","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1002\/emmm.201100671","article-title":"Balancing the fat: lipid droplets and human disease","volume":"5","author":"N Krahmer","year":"2013","journal-title":"EMBO Mol Med"},{"issue":"11","key":"pgen.1009602.ref006","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1194\/jlr.R066597","article-title":"Oxidative stress and lipotoxicity","volume":"57","author":"AK Hauck","year":"2016","journal-title":"J Lipid Res"},{"issue":"4","key":"pgen.1009602.ref007","doi-asserted-by":"crossref","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":"N Krahmer","year":"2011","journal-title":"Cell Metab"},{"issue":"3","key":"pgen.1009602.ref008","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"JA Olzmann","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pgen.1009602.ref009","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1146\/annurev-cellbio-100616-060608","article-title":"Lipid Droplet Biogenesis","volume":"33","author":"TC Walther","year":"2017","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"50","key":"pgen.1009602.ref010","doi-asserted-by":"crossref","first-page":"10747","DOI":"10.1021\/bi1013003","article-title":"Seipin is a discrete homooligomer","volume":"49","author":"D Binns","year":"2010","journal-title":"Biochemistry"},{"issue":"2","key":"pgen.1009602.ref011","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.devcel.2018.09.010","article-title":"Human SEIPIN Binds Anionic Phospholipids","volume":"47","author":"R Yan","year":"2018","journal-title":"Dev Cell"},{"issue":"12","key":"pgen.1009602.ref012","doi-asserted-by":"crossref","first-page":"4080","DOI":"10.1083\/jcb.201809067","article-title":"Cryo-electron microscopy structure of the lipid droplet-formation protein seipin","volume":"217","author":"X Sui","year":"2018","journal-title":"J Cell Biol"},{"issue":"4","key":"pgen.1009602.ref013","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.devcel.2019.05.016","article-title":"Seipin Facilitates Triglyceride Flow to Lipid Droplet and Counteracts Droplet Ripening via Endoplasmic Reticulum Contact","volume":"50","author":"VT Salo","year":"2019","journal-title":"Dev Cell"},{"issue":"4","key":"pgen.1009602.ref014","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/ng585","article-title":"Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13","volume":"28","author":"J Magre","year":"2001","journal-title":"Nat Genet"},{"issue":"9","key":"pgen.1009602.ref015","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrendo.2015.123","article-title":"Congenital generalized lipodystrophies\u2014new insights into metabolic dysfunction","volume":"11","author":"N Patni","year":"2015","journal-title":"Nat Rev Endocrinol"},{"issue":"11","key":"pgen.1009602.ref016","doi-asserted-by":"crossref","first-page":"e292","DOI":"10.1371\/journal.pbio.0060292","article-title":"COPI complex is a regulator of lipid homeostasis","volume":"6","author":"M Beller","year":"2008","journal-title":"PLoS Biol"},{"issue":"7195","key":"pgen.1009602.ref017","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nature06928","article-title":"Functional genomic screen reveals genes involved in lipid-droplet formation and utilization","volume":"453","author":"Y Guo","year":"2008","journal-title":"Nature"},{"issue":"Pt 11","key":"pgen.1009602.ref018","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1242\/jcs.045849","article-title":"Coatomer-dependent protein delivery to lipid droplets","volume":"122","author":"KG Soni","year":"2009","journal-title":"J Cell Sci"},{"key":"pgen.1009602.ref019","doi-asserted-by":"crossref","first-page":"e01607","DOI":"10.7554\/eLife.01607","article-title":"Arf1\/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting","volume":"3","author":"F Wilfling","year":"2014","journal-title":"Elife"},{"issue":"6","key":"pgen.1009602.ref020","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nrgastro.2017.32","article-title":"Lipid droplets and liver disease: from basic biology to clinical implications","volume":"14","author":"NL Gluchowski","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"pgen.1009602.ref021","first-page":"49","article-title":"The lipid droplet-a well-connected organelle","volume":"3","author":"Q Gao","year":"2015","journal-title":"Front Cell Dev Biol"},{"key":"pgen.1009602.ref022","doi-asserted-by":"crossref","first-page":"2515256419896965","DOI":"10.1177\/2515256419896965","article-title":"Duo in a Mystical Realm\u2014Nuclear Lipid Droplets and the Inner Nuclear Membrane","volume":"2","author":"K So\u0142tysik","year":"2019","journal-title":"Contact"},{"issue":"1","key":"pgen.1009602.ref023","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1083\/jcb.201512056","article-title":"Lipid droplets go nuclear","volume":"212","author":"RV Farese","year":"2016","journal-title":"J Cell Biol"},{"issue":"1","key":"pgen.1009602.ref024","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1083\/jcb.201507122","article-title":"PML isoform II plays a critical role in nuclear lipid droplet formation","volume":"212","author":"Y Ohsaki","year":"2016","journal-title":"J Cell Biol"},{"issue":"3","key":"pgen.1009602.ref025","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.cell.2018.05.047","article-title":"The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets","volume":"174","author":"A Romanauska","year":"2018","journal-title":"Cell"},{"issue":"1","key":"pgen.1009602.ref026","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1534\/genetics.116.197160","article-title":"Cell Biology of the Caenorhabditis elegans Nucleus","volume":"205","author":"O Cohen-Fix","year":"2017","journal-title":"Genetics"},{"issue":"11","key":"pgen.1009602.ref027","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1091\/mbc.11.11.3937","article-title":"Essential roles for Caenorhabditis elegans lamin gene in nuclear organization, cell cycle progression, and spatial organization of nuclear pore complexes","volume":"11","author":"J Liu","year":"2000","journal-title":"Mol Biol Cell"},{"issue":"3","key":"pgen.1009602.ref028","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/19491034.2016.1183848","article-title":"The nuclear lamina in health and disease","volume":"7","author":"A Dobrzynska","year":"2016","journal-title":"Nucleus"},{"issue":"5","key":"pgen.1009602.ref029","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1242\/dev.126.5.1011","article-title":"Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline","volume":"126","author":"TL Gumienny","year":"1999","journal-title":"Development"},{"issue":"1","key":"pgen.1009602.ref030","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/advances\/nmy059","article-title":"The Nematode Caenorhabditis elegans as a Model Organism to Study Metabolic Effects of omega-3 Polyunsaturated Fatty Acids in Obesity","volume":"10","author":"A Bouyanfif","year":"2019","journal-title":"Adv Nutr"},{"key":"pgen.1009602.ref031","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1146\/annurev-physiol-021014-071704","article-title":"Regulation of body fat in Caenorhabditis elegans","volume":"77","author":"S Srinivasan","year":"2015","journal-title":"Annu Rev Physiol"},{"issue":"3","key":"pgen.1009602.ref032","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1534\/genetics.115.179127","article-title":"Genetics of Lipid-Storage Management in Caenorhabditis elegans Embryos","volume":"202","author":"V Schmokel","year":"2016","journal-title":"Genetics"},{"issue":"1","key":"pgen.1009602.ref033","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/0012-1606(76)90267-0","article-title":"Development of the reproductive system of Caenorhabditis elegans","volume":"49","author":"D Hirsh","year":"1976","journal-title":"Dev Biol"},{"issue":"1","key":"pgen.1009602.ref034","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0012-1606(83)90322-6","article-title":"Tissue-specific synthesis of yolk proteins in Caenorhabditis elegans","volume":"96","author":"J Kimble","year":"1983","journal-title":"Dev Biol"},{"key":"pgen.1009602.ref035","first-page":"1","article-title":"Germline survival and apoptosis","volume":"2008","author":"A Gartner","journal-title":"WormBook"},{"issue":"1","key":"pgen.1009602.ref036","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ydbio.2007.05.019","article-title":"Differential timing of S phases, X chromosome replication, and meiotic prophase in the C. elegans germ line","volume":"308","author":"A Jaramillo-Lambert","year":"2007","journal-title":"Dev Biol"},{"issue":"2","key":"pgen.1009602.ref037","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1534\/genetics.117.300605","article-title":"HOP-1 Presenilin Deficiency Causes a Late-Onset Notch Signaling Phenotype That Affects Adult Germline Function in Caenorhabditis elegans","volume":"208","author":"I Agarwal","year":"2018","journal-title":"Genetics"},{"issue":"7","key":"pgen.1009602.ref038","doi-asserted-by":"crossref","first-page":"e1007417","DOI":"10.1371\/journal.pgen.1007417","article-title":"Binucleate germ cells in Caenorhabditis elegans are removed by physiological apoptosis","volume":"14","author":"SA Raiders","year":"2018","journal-title":"PLoS Genet"},{"issue":"9","key":"pgen.1009602.ref039","doi-asserted-by":"crossref","first-page":"R194","DOI":"10.1186\/gb-2007-8-9-r194","article-title":"Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection","volume":"8","author":"D Wong","year":"2007","journal-title":"Genome Biol"},{"key":"pgen.1009602.ref040","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/B978-0-12-801430-1.00006-8","article-title":"Necrotic cell death in Caenorhabditis elegans","volume":"545","author":"V Nikoletopoulou","year":"2014","journal-title":"Methods Enzymol"},{"issue":"3","key":"pgen.1009602.ref041","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1474-9726.2008.00375.x","article-title":"Valproic acid extends Caenorhabditis elegans lifespan","volume":"7","author":"K Evason","year":"2008","journal-title":"Aging Cell"},{"issue":"1","key":"pgen.1009602.ref042","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/0012-1606(85)90381-1","article-title":"Polyploid tissues in the nematode Caenorhabditis elegans","volume":"107","author":"EM Hedgecock","year":"1985","journal-title":"Dev Biol"},{"issue":"3","key":"pgen.1009602.ref043","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1152\/physrev.00047.2005","article-title":"Nuclear lamins: laminopathies and their role in premature ageing","volume":"86","author":"JL Broers","year":"2006","journal-title":"Physiol Rev"},{"issue":"6","key":"pgen.1009602.ref044","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.tcb.2011.03.008","article-title":"The nucleoplasmic reticulum: form and function","volume":"21","author":"A Malhas","year":"2011","journal-title":"Trends Cell Biol"},{"issue":"1","key":"pgen.1009602.ref045","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41467-019-08411-x","article-title":"Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis","volume":"10","author":"K Soltysik","year":"2019","journal-title":"Nat Commun"},{"issue":"6","key":"pgen.1009602.ref046","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1091\/mbc.e07-02-0154","article-title":"The nucleolar channel system of human endometrium is related to endoplasmic reticulum and R-rings","volume":"18","author":"N Kittur","year":"2007","journal-title":"Mol Biol Cell"},{"issue":"2","key":"pgen.1009602.ref047","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ydbio.2017.10.004","article-title":"Automated three-dimensional reconstruction of the Caenorhabditis elegans germline","volume":"432","author":"S Gopal","year":"2017","journal-title":"Dev Biol"},{"key":"pgen.1009602.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4614-4015-4_1","article-title":"Introduction to germ cell development in Caenorhabditis elegans","volume":"757","author":"N Pazdernik","year":"2013","journal-title":"Adv Exp Med Biol"},{"issue":"12","key":"pgen.1009602.ref049","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1002\/dvdy.21335","article-title":"The C. elegans germ line: a model for stem cell biology","volume":"236","author":"EJA Hubbard","year":"2007","journal-title":"Developmental dynamics: an official publication of the American Association of Anatomists"},{"issue":"1","key":"pgen.1009602.ref050","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1006\/dbio.1999.9356","article-title":"Ultrastructural features of the adult hermaphrodite gonad of Caenorhabditis elegans: relations between the germ line and soma","volume":"212","author":"DH Hall","year":"1999","journal-title":"Dev Biol"},{"issue":"12","key":"pgen.1009602.ref051","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1091\/mbc.10.12.4311","article-title":"Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte","volume":"10","author":"B Grant","year":"1999","journal-title":"Mol Biol Cell"},{"issue":"1","key":"pgen.1009602.ref052","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ydbio.2012.10.002","article-title":"Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans","volume":"373","author":"CM Webster","year":"2013","journal-title":"Dev Biol"},{"issue":"3","key":"pgen.1009602.ref053","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1534\/genetics.114.168815","article-title":"Two classes of gap junction channels mediate soma-germline interactions essential for germline proliferation and gametogenesis in Caenorhabditis elegans","volume":"198","author":"TA Starich","year":"2014","journal-title":"Genetics"},{"key":"pgen.1009602.ref054","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.58619","article-title":"Gap junctions deliver malonyl-CoA from soma to germline to support embryogenesis in Caenorhabditis elegans","volume":"9","author":"TA Starich","year":"2020","journal-title":"Elife"},{"issue":"13","key":"pgen.1009602.ref055","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1242\/dev.034595","article-title":"Somatic cAMP signaling regulates MSP-dependent oocyte growth and meiotic maturation in C. elegans","volume":"136","author":"JA Govindan","year":"2009","journal-title":"Development"},{"issue":"12","key":"pgen.1009602.ref056","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1242\/dev.004952","article-title":"Actin-dependent cytoplasmic streaming in C. elegans oogenesis","volume":"134","author":"U Wolke","year":"2007","journal-title":"Development"},{"issue":"3","key":"pgen.1009602.ref057","doi-asserted-by":"crossref","first-page":"e1003341","DOI":"10.1371\/journal.pgen.1003341","article-title":"Both the caspase CSP-1 and a caspase-independent pathway promote programmed cell death in parallel to the canonical pathway for apoptosis in Caenorhabditis elegans","volume":"9","author":"DP Denning","year":"2013","journal-title":"PLoS Genet"},{"issue":"1","key":"pgen.1009602.ref058","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/genetics\/119.1.43","article-title":"fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans","volume":"119","author":"T Schedl","year":"1988","journal-title":"Genetics"},{"issue":"1","key":"pgen.1009602.ref059","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1006\/dbio.1998.9109","article-title":"On the control of oocyte meiotic maturation and ovulation in Caenorhabditis elegans","volume":"205","author":"J McCarter","year":"1999","journal-title":"Dev Biol"},{"issue":"5511","key":"pgen.1009602.ref060","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1126\/science.1057586","article-title":"A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation","volume":"291","author":"MA Miller","year":"2001","journal-title":"Science"},{"issue":"19","key":"pgen.1009602.ref061","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.250100","article-title":"Molecular basis for KDEL-mediated retrieval of escaped ER-resident proteins\u2014SWEET talking the COPs","volume":"133","author":"S Newstead","year":"2020","journal-title":"J Cell Sci"},{"issue":"14","key":"pgen.1009602.ref062","doi-asserted-by":"crossref","first-page":"R660","DOI":"10.1016\/j.cub.2014.05.033","article-title":"Connecting the cytoskeleton to the endoplasmic reticulum and Golgi","volume":"24","author":"PS Gurel","year":"2014","journal-title":"Curr Biol"},{"issue":"2","key":"pgen.1009602.ref063","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1083\/jcb.200902101","article-title":"A ZYG-12-dynein interaction at the nuclear envelope defines cytoskeletal architecture in the C. elegans gonad","volume":"186","author":"K Zhou","year":"2009","journal-title":"J Cell Biol"},{"issue":"5","key":"pgen.1009602.ref064","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.tig.2015.02.009","article-title":"The laboratory domestication of Caenorhabditis elegans","volume":"31","author":"MG Sterken","year":"2015","journal-title":"Trends Genet"},{"issue":"8","key":"pgen.1009602.ref065","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1534\/g3.116.030866","article-title":"A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans","volume":"6","author":"S Li","year":"2016","journal-title":"G3 (Bethesda)"},{"issue":"10","key":"pgen.1009602.ref066","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1073\/pnas.0912308107","article-title":"Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans","volume":"107","author":"SO Zhang","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1009602.ref067","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202005026","article-title":"Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner","volume":"220","author":"K Soltysik","year":"2021","journal-title":"J Cell Biol"},{"issue":"1","key":"pgen.1009602.ref068","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1038\/s41467-019-10835-4","article-title":"Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain","volume":"10","author":"Z Cao","year":"2019","journal-title":"Nat Commun"},{"key":"pgen.1009602.ref069","article-title":"Loss of the seipin gene perturbs eggshell formation in C. elegans","author":"X Bai","year":"2020","journal-title":"Development"},{"issue":"2","key":"pgen.1009602.ref070","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ydbio.2008.12.038","article-title":"Involvement of an inner nuclear membrane protein, Nemp1, in Xenopus neural development through an interaction with the chromatin protein BAF","volume":"327","author":"H Mamada","year":"2009","journal-title":"Dev Biol"},{"issue":"1","key":"pgen.1009602.ref071","doi-asserted-by":"crossref","first-page":"M110 003129","DOI":"10.1074\/mcp.M110.003129","article-title":"Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations","volume":"10","author":"GS Wilkie","year":"2011","journal-title":"Mol Cell Proteomics"},{"issue":"35","key":"pgen.1009602.ref072","doi-asserted-by":"crossref","first-page":"eabb4591","DOI":"10.1126\/sciadv.abb4591","article-title":"The NEMP family supports metazoan fertility and nuclear envelope stiffness","volume":"6","author":"Y Tsatskis","year":"2020","journal-title":"Sci Adv"},{"issue":"6","key":"pgen.1009602.ref073","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s10528-019-09926-0","article-title":"NEMP1 Promotes Tamoxifen Resistance in Breast Cancer Cells","volume":"57","author":"Y Liu","year":"2019","journal-title":"Biochem Genet"},{"issue":"5","key":"pgen.1009602.ref074","doi-asserted-by":"crossref","first-page":"e0127271","DOI":"10.1371\/journal.pone.0127271","article-title":"The Inner Nuclear Membrane Protein Nemp1 Is a New Type of RanGTP-Binding Protein in Eukaryotes","volume":"10","author":"T Shibano","year":"2015","journal-title":"PLoS One"},{"issue":"5","key":"pgen.1009602.ref075","article-title":"Towards a mechanistic understanding of lipodystrophy and seipin functions","volume":"34","author":"K Wee","year":"2014","journal-title":"Biosci Rep"},{"issue":"5","key":"pgen.1009602.ref076","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.209890","article-title":"Formation of COPI-coated vesicles at a glance","volume":"131","author":"EC Arakel","year":"2018","journal-title":"J Cell Sci"},{"issue":"7","key":"pgen.1009602.ref077","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/emboj.2013.41","article-title":"Rules for the recognition of dilysine retrieval motifs by coatomer","volume":"32","author":"W Ma","year":"2013","journal-title":"EMBO J"},{"issue":"6","key":"pgen.1009602.ref078","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.devcel.2012.10.017","article-title":"Molecular basis for recognition of dilysine trafficking motifs by COPI","volume":"23","author":"LP Jackson","year":"2012","journal-title":"Dev Cell"},{"issue":"10","key":"pgen.1009602.ref079","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1101\/gr.157651.113","article-title":"The million mutation project: a new approach to genetics in Caenorhabditis elegans","volume":"23","author":"O Thompson","year":"2013","journal-title":"Genome Res"},{"issue":"D1","key":"pgen.1009602.ref080","first-page":"D762","article-title":"WormBase: a modern Model Organism Information Resource","volume":"48","author":"TW Harris","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"33","key":"pgen.1009602.ref081","doi-asserted-by":"crossref","first-page":"22774","DOI":"10.1074\/jbc.M801869200","article-title":"Scyl1, mutated in a recessive form of spinocerebellar neurodegeneration, regulates COPI-mediated retrograde traffic","volume":"283","author":"JL Burman","year":"2008","journal-title":"J Biol Chem"},{"key":"pgen.1009602.ref082","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/1471-2164-13-333","article-title":"A survey of putative secreted and transmembrane proteins encoded in the C. elegans genome","volume":"13","author":"J Suh","year":"2012","journal-title":"BMC Genomics"},{"issue":"9","key":"pgen.1009602.ref083","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/emboj.2013.77","article-title":"Mitochondria-type GPAT is required for mitochondrial fusion","volume":"32","author":"Y Ohba","year":"2013","journal-title":"EMBO J"},{"issue":"10","key":"pgen.1009602.ref084","doi-asserted-by":"crossref","first-page":"e7545","DOI":"10.1371\/journal.pone.0007545","article-title":"The influence of bacterial diet on fat storage in C. elegans","volume":"4","author":"KK Brooks","year":"2009","journal-title":"PLoS One"},{"issue":"6","key":"pgen.1009602.ref085","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1016\/j.cell.2014.02.036","article-title":"Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits","volume":"156","author":"E Watson","year":"2014","journal-title":"Cell"},{"key":"pgen.1009602.ref086","first-page":"4","article-title":"C. elegans outside the Petri dish","author":"L Frezal","year":"2015","journal-title":"Elife"},{"issue":"9","key":"pgen.1009602.ref087","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1091\/mbc.e06-10-0973","article-title":"The size of the nucleus increases as yeast cells grow","volume":"18","author":"P Jorgensen","year":"2007","journal-title":"Mol Biol Cell"},{"key":"pgen.1009602.ref088","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev-cellbio-020520-120627","article-title":"Nuclear Membrane Rupture and Its Consequences","volume":"36","author":"J Maciejowski","year":"2020","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"8","key":"pgen.1009602.ref089","doi-asserted-by":"crossref","DOI":"10.3390\/cells9081884","article-title":"Structural and Mechanical Aberrations of the Nuclear Lamina in Disease","volume":"9","author":"M Stiekema","year":"2020","journal-title":"Cells"},{"issue":"1","key":"pgen.1009602.ref090","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1080\/19491034.2020.1815410","article-title":"Nuclear membrane ruptures, cell death, and tissue damage in the setting of nuclear lamin deficiencies","volume":"11","author":"NY Chen","year":"2020","journal-title":"Nucleus"},{"key":"pgen.1009602.ref091","first-page":"6","article-title":"Genetic defects in beta-spectrin and tau sensitize C. elegans axons to movement-induced damage via torque-tension coupling","author":"M Krieg","year":"2017","journal-title":"Elife"},{"issue":"7","key":"pgen.1009602.ref092","doi-asserted-by":"crossref","first-page":"680","DOI":"10.4161\/epi.20540","article-title":"Global heterochromatin loss: a unifying theory of aging?","volume":"7","author":"A Tsurumi","year":"2012","journal-title":"Epigenetics"},{"key":"pgen.1009602.ref093","first-page":"8","article-title":"A multiplexed DNA FISH strategy for assessing genome architecture in Caenorhabditis elegans","author":"BD Fields","year":"2019","journal-title":"Elife"},{"issue":"46","key":"pgen.1009602.ref094","doi-asserted-by":"crossref","first-page":"16690","DOI":"10.1073\/pnas.0506955102","article-title":"Age-related changes of nuclear architecture in Caenorhabditis elegans","volume":"102","author":"E Haithcock","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pgen.1009602.ref095","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41418-018-0266-5","article-title":"Nucleophagy: from homeostasis to disease","volume":"26","author":"ME Papandreou","year":"2019","journal-title":"Cell Death Differ"},{"issue":"12","key":"pgen.1009602.ref096","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1038\/ncb3641","article-title":"A transient pool of nuclear F-actin at mitotic exit controls chromatin organization","volume":"19","author":"C Baarlink","year":"2017","journal-title":"Nat Cell Biol"},{"issue":"3","key":"pgen.1009602.ref097","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.devcel.2020.01.019","article-title":"How Genes Move: Spatial Repositioning of Activated Genes Is Driven by Nuclear Actin-Based Pathway","volume":"52","author":"M Capelson","year":"2020","journal-title":"Dev Cell"},{"key":"pgen.1009602.ref098","first-page":"111714","article-title":"Nuclear actin: The new normal","volume":"821","author":"L Serebryannyy","journal-title":"Mutat Res. 2020"},{"issue":"12","key":"pgen.1009602.ref099","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/ar.23959","article-title":"Nuclear Actin: From Discovery to Function","volume":"301","author":"DJ Kelpsch","year":"2018","journal-title":"Anat Rec (Hoboken)"},{"issue":"3","key":"pgen.1009602.ref100","doi-asserted-by":"crossref","first-page":"264","DOI":"10.4161\/nucl.11799","article-title":"Direct actin binding to A- and B-type lamin tails and actin filament bundling by the lamin A tail","volume":"1","author":"DN Simon","year":"2010","journal-title":"Nucleus"},{"issue":"4","key":"pgen.1009602.ref101","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1101\/gr.196220.115","article-title":"A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha","volume":"26","author":"K Gesson","year":"2016","journal-title":"Genome Res"},{"issue":"4","key":"pgen.1009602.ref102","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1111\/j.1474-9726.2011.00713.x","article-title":"Loss of intestinal nuclei and intestinal integrity in aging C. elegans","volume":"10","author":"MD McGee","year":"2011","journal-title":"Aging Cell"},{"issue":"7","key":"pgen.1009602.ref103","doi-asserted-by":"crossref","first-page":"e1001613","DOI":"10.1371\/journal.pbio.1001613","article-title":"Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans","volume":"11","author":"C Coburn","year":"2013","journal-title":"PLoS Biol"},{"issue":"7288","key":"pgen.1009602.ref104","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature08980","article-title":"The genetics of ageing","volume":"464","author":"CJ Kenyon","year":"2010","journal-title":"Nature"},{"issue":"4","key":"pgen.1009602.ref105","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0092-8674(03)00889-4","article-title":"Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan","volume":"115","author":"N Libina","year":"2003","journal-title":"Cell"},{"issue":"20","key":"pgen.1009602.ref106","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1016\/j.cub.2018.10.003","article-title":"C. elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent Pathologies","volume":"28","author":"M Ezcurra","year":"2018","journal-title":"Curr Biol"},{"issue":"12","key":"pgen.1009602.ref107","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1101\/gr.083055.108","article-title":"Genome-scale spatiotemporal analysis of Caenorhabditis elegans microRNA promoter activity","volume":"18","author":"NJ Martinez","year":"2008","journal-title":"Genome Res"},{"issue":"6283","key":"pgen.1009602.ref108","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.aad7297","article-title":"Nuclear envelope rupture and repair during cancer cell migration","volume":"352","author":"CM Denais","year":"2016","journal-title":"Science"},{"key":"pgen.1009602.ref109","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ceb.2014.01.006","article-title":"Traffic to the inner membrane of the nuclear envelope","volume":"28","author":"JK Laba","year":"2014","journal-title":"Curr Opin Cell Biol"},{"key":"pgen.1009602.ref110","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1146\/annurev-biochem-061009-102430","article-title":"Lipid droplets and cellular lipid metabolism","volume":"81","author":"TC Walther","year":"2012","journal-title":"Annu Rev Biochem"},{"issue":"1","key":"pgen.1009602.ref111","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0012-1606(76)90119-6","article-title":"The life cycle of the nematode Caenorhabditis elegans. I. Wild-type growth and reproduction","volume":"51","author":"L Byerly","year":"1976","journal-title":"Dev Biol"},{"issue":"5","key":"pgen.1009602.ref112","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1091\/mbc.e04-08-0726","article-title":"Involvement of the actin cytoskeleton and homotypic membrane fusion in ER dynamics in Caenorhabditis elegans","volume":"16","author":"D Poteryaev","year":"2005","journal-title":"Mol Biol Cell"},{"issue":"1","key":"pgen.1009602.ref113","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"S Brenner","year":"1974","journal-title":"Genetics"},{"issue":"5","key":"pgen.1009602.ref114","doi-asserted-by":"crossref","first-page":"B215","DOI":"10.1093\/gerona\/55.5.B215","article-title":"Defining wild-type life span in Caenorhabditis elegans","volume":"55","author":"D Gems","year":"2000","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"33","key":"pgen.1009602.ref115","doi-asserted-by":"crossref","first-page":"23606","DOI":"10.1074\/jbc.M513589200","article-title":"Hemicentin assembly in the extracellular matrix is mediated by distinct structural modules","volume":"281","author":"C Dong","year":"2006","journal-title":"J Biol Chem"},{"issue":"8","key":"pgen.1009602.ref116","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1242\/dev.044255","article-title":"Perinuclear P granules are the principal sites of mRNA export in adult C. elegans germ cells","volume":"137","author":"U Sheth","year":"2010","journal-title":"Development"},{"issue":"6920","key":"pgen.1009602.ref117","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature01278","article-title":"Systematic functional analysis of the Caenorhabditis elegans genome using RNAi","volume":"421","author":"RS Kamath","year":"2003","journal-title":"Nature"},{"issue":"4","key":"pgen.1009602.ref118","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1101\/gad.1775409","article-title":"Rictor\/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans","volume":"23","author":"AA Soukas","year":"2009","journal-title":"Genes Dev"},{"key":"pgen.1009602.ref119","volume-title":"Principles and Techniques of Electon Microscopy: Biological Appications","author":"MA Hyat","year":"2000","edition":"4"},{"issue":"3","key":"pgen.1009602.ref120","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1534\/genetics.120.303564","article-title":"Melting dsDNA Donor Molecules Greatly Improves Precision Genome Editing in Caenorhabditis elegans","volume":"216","author":"KS Ghanta","year":"2020","journal-title":"Genetics"},{"key":"pgen.1009602.ref121","author":"H Li","year":"2013","journal-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM"},{"issue":"9","key":"pgen.1009602.ref122","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"A McKenna","year":"2010","journal-title":"Genome Res"},{"issue":"2","key":"pgen.1009602.ref123","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"P Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"issue":"5","key":"pgen.1009602.ref124","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.cmet.2009.10.002","article-title":"C. elegans major fats are stored in vesicles distinct from lysosome-related organelles","volume":"10","author":"EJ O\u2019Rourke","year":"2009","journal-title":"Cell Metab"},{"issue":"5","key":"pgen.1009602.ref125","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1091\/mbc.01-10-0514","article-title":"Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in invertebrate neurons","volume":"13","author":"MM Rolls","year":"2002","journal-title":"Mol Biol Cell"},{"issue":"17","key":"pgen.1009602.ref126","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1038\/emboj.2009.204","article-title":"An ER-resident membrane protein complex regulates nicotinic acetylcholine receptor subunit composition at the synapse","volume":"28","author":"RB Almedom","year":"2009","journal-title":"EMBO J"},{"issue":"47","key":"pgen.1009602.ref127","doi-asserted-by":"crossref","first-page":"49243","DOI":"10.1074\/jbc.M405915200","article-title":"FVT-1 is a mammalian 3-ketodihydrosphingosine reductase with an active site that faces the cytosolic side of the endoplasmic reticulum membrane","volume":"279","author":"A Kihara","year":"2004","journal-title":"J Biol Chem"},{"issue":"5","key":"pgen.1009602.ref128","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1242\/dev.129.5.1185","article-title":"A novel thioredoxin-like protein encoded by the C. elegans dpy-11 gene is required for body and sensory organ morphogenesis","volume":"129","author":"FC Ko","year":"2002","journal-title":"Development"},{"issue":"1","key":"pgen.1009602.ref129","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.abb.2003.11.003","article-title":"TMX, a human transmembrane oxidoreductase of the thioredoxin family: the possible role in disulfide-linked protein folding in the endoplasmic reticulum","volume":"423","author":"Y Matsuo","year":"2004","journal-title":"Arch Biochem Biophys"},{"issue":"1","key":"pgen.1009602.ref130","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1534\/g3.115.021915","article-title":"Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans","volume":"6","author":"AS Tam","year":"2015","journal-title":"G3 (Bethesda)"},{"issue":"1","key":"pgen.1009602.ref131","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ydbio.2017.06.019","article-title":"Identification of regulators of germ stem cell enwrapment by its niche in C. elegans","volume":"429","author":"LM Linden","year":"2017","journal-title":"Dev Biol"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T17:27:03Z","timestamp":1623864423000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009602"}},"subtitle":[],"editor":[{"given":"Jennifer L.","family":"Watts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,16]]},"references-count":131,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1009602","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,16]]}}}