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Seipin forms a flexible cage at lipid droplet formation sites.

Arlt H, Sui X, Folger B, Adams C, Chen X, Remme R, Hamprecht FA, DiMaio F, Liao M, Goodman JM, Farese RV, Walther TC
Nat Struct Mol Biol 29 194-202 (2022)
Cited: 20 times
EuropePMC logo PMID: 35210614

Abstract

Lipid droplets (LDs) form in the endoplasmic reticulum by phase separation of neutral lipids. This process is facilitated by the seipin protein complex, which consists of a ring of seipin monomers, with a yet unclear function. Here, we report a structure of S. cerevisiae seipin based on cryogenic-electron microscopy and structural modeling data. Seipin forms a decameric, cage-like structure with the lumenal domains forming a stable ring at the cage floor and transmembrane segments forming the cage sides and top. The transmembrane segments interact with adjacent monomers in two distinct, alternating conformations. These conformations result from changes in switch regions, located between the lumenal domains and the transmembrane segments, that are required for seipin function. Our data indicate a model for LD formation in which a closed seipin cage enables triacylglycerol phase separation and subsequently switches to an open conformation to allow LD growth and budding.

Reviews - 7rsl mentioned but not cited (1)

  1. Structure and function of lipid droplet assembly complexes. Walther TC, Kim S, Arlt H, Voth GA, Farese RV. Curr Opin Struct Biol 80 102606 (2023)

Articles - 7rsl mentioned but not cited (1)

  1. Seipin forms a flexible cage at lipid droplet formation sites. Arlt H, Sui X, Folger B, Adams C, Chen X, Remme R, Hamprecht FA, DiMaio F, Liao M, Goodman JM, Farese RV, Walther TC. Nat Struct Mol Biol 29 194-202 (2022)


Reviews citing this publication (11)

  1. Lipid droplet biogenesis and functions in health and disease. Zadoorian A, Du X, Yang H. Nat Rev Endocrinol 19 443-459 (2023)
  2. Computational Studies of Lipid Droplets. Kim S, Swanson JMJ, Voth GA. J Phys Chem B 126 2145-2154 (2022)
  3. Role of Seipin in Human Diseases and Experimental Animal Models. Li Y, Yang X, Peng L, Xia Q, Zhang Y, Huang W, Liu T, Jia D. Biomolecules 12 840 (2022)
  4. The (social) lives, deaths, and biophysical phases of lipid droplets. Henne WM. Curr Opin Cell Biol 82 102178 (2023)
  5. Insights Into the Biogenesis and Emerging Functions of Lipid Droplets From Unbiased Molecular Profiling Approaches. Sánchez-Álvarez M, Del Pozo MÁ, Bosch M, Pol A. Front Cell Dev Biol 10 901321 (2022)
  6. Seipin-still a mysterious protein? Salo VT. Front Cell Dev Biol 11 1112954 (2023)
  7. Concept of lipid droplet biogenesis. Kumari RM, Khatri A, Chaudhary R, Choudhary V. Eur J Cell Biol 102 151362 (2023)
  8. Early steps in the birth of four membrane-bound organelles-Peroxisomes, lipid droplets, lipoproteins, and autophagosomes. Banerjee S, Prinz WA. Curr Opin Cell Biol 84 102210 (2023)
  9. Intracellular lipase and regulation of the lipid droplet. Cabodevilla AG, Son N, Goldberg IJ. Curr Opin Lipidol 35 85-92 (2024)
  10. Lipid droplets and cellular lipid flux. Mathiowetz AJ, Olzmann JA. Nat Cell Biol 26 331-345 (2024)
  11. [Research Progress of Cellular Lipid Droplets in Oral Diseases]. Xu S, Wei J, Xie J. Sichuan Da Xue Xue Bao Yi Xue Ban 55 475-481 (2024)

Articles citing this publication (7)

  1. Identification of two pathways mediating protein targeting from ER to lipid droplets. Song J, Mizrak A, Lee CW, Cicconet M, Lai ZW, Tang WC, Lu CH, Mohr SE, Farese RV, Walther TC. Nat Cell Biol 24 1364-1377 (2022)
  2. Seipin transmembrane segments critically function in triglyceride nucleation and lipid droplet budding from the membrane. Kim S, Chung J, Arlt H, Pak AJ, Farese RV, Walther TC, Voth GA. Elife 11 e75808 (2022)
  3. Cholesterol esters form supercooled lipid droplets whose nucleation is facilitated by triacylglycerols. Dumesnil C, Vanharanta L, Prasanna X, Omrane M, Carpentier M, Bhapkar A, Enkavi G, Salo VT, Vattulainen I, Ikonen E, Thiam AR. Nat Commun 14 915 (2023)
  4. Seipin concentrates distinct neutral lipids via interactions with their acyl chain carboxyl esters. Renne MF, Corey RA, Ferreira JV, Stansfeld PJ, Stansfeld PJ, Carvalho P. J Cell Biol 221 e202112068 (2022)
  5. ISG15 Is a Novel Regulator of Lipid Metabolism during Vaccinia Virus Infection. Albert M, Vázquez J, Falcón-Pérez JM, Balboa MA, Liesa M, Balsinde J, Guerra S. Microbiol Spectr 10 e0389322 (2022)
  6. PI(3)P and DFCP1 regulate the biogenesis of lipid droplets. Lukmantara I, Chen F, Mak HY, Zadoorian A, Du X, Xiao FN, Norris DM, Pandzic E, Whan R, Zhong Q, Yang H. Mol Biol Cell 33 ar131 (2022)
  7. Editorial Editorial: The evolving role of lipid droplets: Advancements and future directions. Choudhary V, Goodman JM. Front Cell Dev Biol 11 1175083 (2023)


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