Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner
Nuclear lipid droplets (LDs) in hepatocytes are derived from precursors of very-low-density lipoprotein in the ER lumen, but it is not known how cells lacking the lipoprotein secretory function form nuclear LDs. Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride s...
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| Veröffentlicht in: | The Journal of cell biology 2021-01, Vol.220 (1) |
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| container_title | The Journal of cell biology |
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| creator | Sołtysik, Kamil Ohsaki, Yuki Tatematsu, Tsuyako Cheng, Jinglei Maeda, Asami Morita, Shin-Ya Fujimoto, Toyoshi |
| description | Nuclear lipid droplets (LDs) in hepatocytes are derived from precursors of very-low-density lipoprotein in the ER lumen, but it is not known how cells lacking the lipoprotein secretory function form nuclear LDs. Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride synthesis enzymes, including ACSL3, AGPAT2, GPAT3/GPAT4, and DGAT1/DGAT2, and generates nuclear LDs in situ. mTOR inhibition increases nuclear LDs by inducing the nuclear translocation of lipin-1 phosphatidic acid (PA) phosphatase. Seipin, a protein essential for normal cytoplasmic LD formation in the ER, is absent in the INM. Knockdown of seipin increases nuclear LDs and PA in the nucleus, whereas seipin overexpression decreases these. Seipin knockdown also up-regulates lipin-1β expression, and lipin-1 knockdown decreases the effect of seipin knockdown on nuclear LDs without affecting PA redistribution. These results indicate that seipin is not directly involved in nuclear LD formation but instead restrains it by affecting lipin-1 expression and intracellular PA distribution. |
| doi_str_mv | 10.1083/jcb.202005026 |
| format | Article |
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Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride synthesis enzymes, including ACSL3, AGPAT2, GPAT3/GPAT4, and DGAT1/DGAT2, and generates nuclear LDs in situ. mTOR inhibition increases nuclear LDs by inducing the nuclear translocation of lipin-1 phosphatidic acid (PA) phosphatase. Seipin, a protein essential for normal cytoplasmic LD formation in the ER, is absent in the INM. Knockdown of seipin increases nuclear LDs and PA in the nucleus, whereas seipin overexpression decreases these. Seipin knockdown also up-regulates lipin-1β expression, and lipin-1 knockdown decreases the effect of seipin knockdown on nuclear LDs without affecting PA redistribution. These results indicate that seipin is not directly involved in nuclear LD formation but instead restrains it by affecting lipin-1 expression and intracellular PA distribution.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.202005026</identifier><identifier>PMID: 33315072</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Biochemistry ; Droplets ; Hepatocytes ; Lipids ; Membrane and Lipid Biology ; Membranes ; Metabolism ; Nuclear transport ; Organelles ; Phosphatidic acid ; TOR protein ; Translocation ; Triglycerides</subject><ispartof>The Journal of cell biology, 2021-01, Vol.220 (1)</ispartof><rights>2020 Sołtysik et al.</rights><rights>Copyright Rockefeller University Press Jan 2021</rights><rights>2020 Sołtysik et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-4968bbf28bae005b135d29cdabbeca7bd781d7c9d5ec94163a85fa9d735cc7213</citedby><cites>FETCH-LOGICAL-c481t-4968bbf28bae005b135d29cdabbeca7bd781d7c9d5ec94163a85fa9d735cc7213</cites><orcidid>0000-0002-1539-6461 ; 0000-0002-3601-7977 ; 0000-0003-4079-707X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33315072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sołtysik, Kamil</creatorcontrib><creatorcontrib>Ohsaki, Yuki</creatorcontrib><creatorcontrib>Tatematsu, Tsuyako</creatorcontrib><creatorcontrib>Cheng, Jinglei</creatorcontrib><creatorcontrib>Maeda, Asami</creatorcontrib><creatorcontrib>Morita, Shin-Ya</creatorcontrib><creatorcontrib>Fujimoto, Toyoshi</creatorcontrib><title>Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Nuclear lipid droplets (LDs) in hepatocytes are derived from precursors of very-low-density lipoprotein in the ER lumen, but it is not known how cells lacking the lipoprotein secretory function form nuclear LDs. Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride synthesis enzymes, including ACSL3, AGPAT2, GPAT3/GPAT4, and DGAT1/DGAT2, and generates nuclear LDs in situ. mTOR inhibition increases nuclear LDs by inducing the nuclear translocation of lipin-1 phosphatidic acid (PA) phosphatase. Seipin, a protein essential for normal cytoplasmic LD formation in the ER, is absent in the INM. Knockdown of seipin increases nuclear LDs and PA in the nucleus, whereas seipin overexpression decreases these. Seipin knockdown also up-regulates lipin-1β expression, and lipin-1 knockdown decreases the effect of seipin knockdown on nuclear LDs without affecting PA redistribution. These results indicate that seipin is not directly involved in nuclear LD formation but instead restrains it by affecting lipin-1 expression and intracellular PA distribution.</description><subject>Biochemistry</subject><subject>Droplets</subject><subject>Hepatocytes</subject><subject>Lipids</subject><subject>Membrane and Lipid Biology</subject><subject>Membranes</subject><subject>Metabolism</subject><subject>Nuclear transport</subject><subject>Organelles</subject><subject>Phosphatidic acid</subject><subject>TOR protein</subject><subject>Translocation</subject><subject>Triglycerides</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpdkc1r3DAQxUVJaDbbHnMNglx6cTr6suRLoYS2CYTmkkBuQl_OerFlV7ID_e-jJZul6UUDmt885s1D6IzAJQHFvm6dvaRAAQTQ-gNaEcGhUoTDEVoBUFI1gooTdJrzFgC45OwjOmGMEQGSrtDj78X1wSTcd1PnsU_j1Ic543ZMA-4injehlBgSjntwCINNJu6-scE5lLlYddGHKZQnzngwO_4TOm5Nn8PnfV2jh58_7q-uq9u7XzdX328rxxWZK97UytqWKmtC8WAJE542zhtrgzPSeqmIl67xIriGk5oZJVrTeMmEc5IStkbfXnWnxQ7Bu7JBMr2eUjeY9FePptPvO7Hb6KfxWUvJpARWBL7sBdL4Zwl51kOXXej74nFcsqZcljs2UO_Qi__Q7bikWOwVStWkIVzJQlWvlEtjzim0h2UI6F1mumSmD5kV_vxfBwf6LST2ArOWk5s</recordid><startdate>20210104</startdate><enddate>20210104</enddate><creator>Sołtysik, Kamil</creator><creator>Ohsaki, Yuki</creator><creator>Tatematsu, Tsuyako</creator><creator>Cheng, Jinglei</creator><creator>Maeda, Asami</creator><creator>Morita, Shin-Ya</creator><creator>Fujimoto, Toyoshi</creator><general>Rockefeller University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1539-6461</orcidid><orcidid>https://orcid.org/0000-0002-3601-7977</orcidid><orcidid>https://orcid.org/0000-0003-4079-707X</orcidid></search><sort><creationdate>20210104</creationdate><title>Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner</title><author>Sołtysik, Kamil ; 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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Biochemistry Droplets Hepatocytes Lipids Membrane and Lipid Biology Membranes Metabolism Nuclear transport Organelles Phosphatidic acid TOR protein Translocation Triglycerides |
| title | Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner |
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