title: Seipin is required for converting nascent to mature lipid droplets.
abstract: How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. UsingDrosophilaand human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States.|Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Huajin
authors: H
authors: Wang
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Michel
authors: M
authors: Becuwe
authors: Department of Genetics, Harvard Medical School, Boston, United States.
authors: Benjamin E
authors: BE
authors: Housden
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Chandramohan
authors: C
authors: Chitraju
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Ashley J
authors: AJ
authors: Porras
authors: Center for Cellular and Molecular Imaging, Department of Cell Biology, Yale School of Medicine, New Haven, United States.
authors: Morven M
authors: MM
authors: Graham
authors: Center for Cellular and Molecular Imaging, Department of Cell Biology, Yale School of Medicine, New Haven, United States.
authors: Xinran N
authors: XN
authors: Liu
authors: Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Univ Paris 06, CNRS UMR 8550, Paris, France.
authors: Abdou Rachid
authors: AR
authors: Thiam
authors: The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom.
authors: David B
authors: DB
authors: Savage
authors: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, United States.
authors: Anil K
authors: AK
authors: Agarwal
authors: Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, United States.
authors: Abhimanyu
authors: A
authors: Garg
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Maria-Jesus
authors: MJ
authors: Olarte
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors: Qingqing
authors: Q
authors: Lin
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.|Molecular Membrane Biology Section, Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany.
authors: Florian
authors: F
authors: Fröhlich
authors: VILLUM Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors: Hans Kristian
authors: HK
authors: Hannibal-Bach
authors: Department of Cell Biology, Harvard Medical School, Boston, United States.|Department of Pediatrics, Harvard Medical School, Boston, United States.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States.
authors: Srigokul
authors: S
authors: Upadhyayula
authors: Department of Genetics, Harvard Medical School, Boston, United States.|Howard Hughes Medical Institute, Boston, United States.
authors: Norbert
authors: N
authors: Perrimon
authors: Department of Cell Biology, Harvard Medical School, Boston, United States.|Department of Pediatrics, Harvard Medical School, Boston, United States.|Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States.
authors: Tomas
authors: T
authors: Kirchhausen
authors: VILLUM Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors: Christer S
authors: CS
authors: Ejsing
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.|Howard Hughes Medical Institute, Boston, United States.|Broad Institute of Harvard and MIT, Cambridge, United States.
authors: Tobias C
authors: TC
authors: Walther
authors: Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.|Department of Cell Biology, Harvard Medical School, Boston, United States.|Broad Institute of Harvard and MIT, Cambridge, United States.
authors: Robert V
authors: http://orcid.org/0000-0001-8103-2239
authors: RV
authors: Farese
keywords: D. melanogaster; LiveDrop; cell biology; endoplasmic reticulum; human; lipid droplet; lipid metabolism; organelle biogenesis; seipin