A Proximity Labeling Strategy Provides Insights into the Composition and Dynamics of Lipid Droplet Proteomes

Dev Cell. 2018 Jan 8;44(1):97-112.e7. doi: 10.1016/j.devcel.2017.11.020. Epub 2017 Dec 21.


Lipid droplet (LD) functions are regulated by a complement of integral and peripheral proteins that associate with the bounding LD phospholipid monolayer. Defining the composition of the LD proteome has remained a challenge due to the presence of contaminating proteins in LD-enriched buoyant fractions. To overcome this limitation, we developed a proximity labeling strategy that exploits LD-targeted APEX2 to biotinylate LD proteins in living cells. Application of this approach to two different cell types identified the vast majority of previously validated LD proteins, excluded common contaminating proteins, and revealed new LD proteins. Moreover, quantitative analysis of LD proteome dynamics uncovered a role for endoplasmic reticulum-associated degradation in controlling the composition of the LD proteome. These data provide an important resource for future LD studies and demonstrate the utility of proximity labeling to study the regulation of LD proteomes.

Keywords: APEX; APEX2; ERAD; biotinylation; endoplasmic reticulum; lipid droplet; proteasome; proteome; proximity labeling; ubiquitin.

Publication types

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

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Biomarkers / metabolism*
  • Carrier Proteins / metabolism
  • Endoplasmic Reticulum-Associated Degradation / physiology*
  • Humans
  • Lipid Droplets / metabolism*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins
  • Proteome / analysis
  • Proteome / metabolism*
  • Receptors, Autocrine Motility Factor / metabolism
  • Staining and Labeling / methods*


  • AKAIN1 protein, human
  • Biomarkers
  • Carrier Proteins
  • DERL1 protein, human
  • Membrane Proteins
  • Membrane Transport Proteins
  • Proteome
  • AMFR protein, human
  • Receptors, Autocrine Motility Factor
  • ATPases Associated with Diverse Cellular Activities