LDAF1 and Seipin Form a Lipid Droplet Assembly Complex

Dev Cell. 2019 Dec 2;51(5):551-563.e7. doi: 10.1016/j.devcel.2019.10.006. Epub 2019 Nov 7.

Abstract

Lipid droplets (LDs) originate from the endoplasmic reticulum (ER) to store triacylglycerol (TG) and cholesterol esters. The ER protein seipin was shown to localize to ER-LD contacts soon after LDs form, but what determines the sites of initial LD biogenesis in the ER is unknown. Here, we identify TMEM159, now re-named lipid droplet assembly factor 1 (LDAF1), as an interaction partner of seipin. Together, LDAF1 and seipin form an ∼600 kDa oligomeric complex that copurifies with TG. LDs form at LDAF1-seipin complexes, and re-localization of LDAF1 to the plasma membrane co-recruits seipin and redirects LD formation to these sites. Once LDs form, LDAF1 dissociates from seipin and moves to the LD surface. In the absence of LDAF1, LDs form only at significantly higher cellular TG concentrations. Our data suggest that the LDAF1-seipin complex is the core protein machinery that facilitates LD biogenesis and determines the sites of their formation in the ER.

Keywords: Berardinelli-Seip congenital lipodystrophy type 2; TMEM159; endoplasmic reticulum; fat; lipid droplets; lipodystrophy; organelle biogenesis; promethin; triacylglycerol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Endoplasmic Reticulum / metabolism
  • GTP-Binding Protein gamma Subunits / metabolism*
  • HEK293 Cells
  • Humans
  • Lipid Droplets / metabolism*
  • Membrane Proteins / metabolism*
  • Protein Binding
  • Triglycerides / metabolism

Substances

  • BSCL2 protein, human
  • GTP-Binding Protein gamma Subunits
  • Membrane Proteins
  • TMEM159 protein, human
  • Triglycerides