title: Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes.
abstract: Mature white adipocytes contain a characteristic unilocular lipid droplet. However, the molecular mechanisms underlying unilocular lipid droplet formation are poorly understood. We previously showed that Fsp27, an adipocyte-specific lipid droplet-associated protein, promotes lipid droplet growth by initiating lipid exchange and transfer. Here, we identify Perilipin1 (Plin1), another adipocyte-specific lipid droplet-associated protein, as an Fsp27 activator. Plin1 interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer and lipid droplet growth. Functional cooperation between Plin1 and Fsp27 is required for efficient lipid droplet growth in adipocytes, as depletion of either protein impairs lipid droplet growth. The CIDE-N domain of Fsp27 forms homodimers and disruption of CIDE-N homodimerization abolishes Fsp27-mediated lipid exchange and transfer. Interestingly, Plin1 can restore the activity of CIDE-N homodimerization-defective mutants of Fsp27. We thus uncover a novel mechanism underlying lipid droplet growth and unilocular lipid droplet formation that involves the cooperative action of Fsp27 and Plin1 in adipocytes.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Sun
authors.forename: Jingyi
authors.initials: J
authors.lastname: Gong
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.forename: Wenyi
authors.initials: W
authors.lastname: Xu
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wu
authors.forename: Dijin
authors.initials: D
authors.lastname: Xu
authors.forename: Jinlan
authors.initials: J
authors.lastname: Gao
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Wu
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D036681:Fluorescence Recovery After Photobleaching; D055785:Gene Knockdown Techniques; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008055:Lipids; C000602978:PLIN1 protein, human; D000070778:Perilipin-1; D010750:Phosphoproteins; C000602979:Plin1 protein, mouse; D011506:Proteins; C525805:fat-specific protein 27, mouse