LDAF1 and Seipin Form a Lipid Droplet Assembly Complex

Jeeyun Chung; Xudong Wu; Talley J Lambert; Zon Weng Lai; Tobias C Walther; Robert V Farese Jr

doi:10.1016/j.devcel.2019.10.006

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.

Authors

Jeeyun Chung¹, Xudong Wu², Talley J Lambert³, Zon Weng Lai⁴, Tobias C Walther⁵, Robert V Farese Jr⁶

Affiliations

¹ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
² Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
³ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
⁴ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Advanced Multi-omics Platform, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁵ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Advanced Multi-omics Platform, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02124, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address: twalther@hsph.harvard.edu.
⁶ Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02124, USA. Electronic address: robert@hsph.harvard.edu.

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding