The surface of lipid droplets constitutes a barrier for endoplasmic reticulum-resident integral membrane proteins

Rasha Khaddaj, Muriel Mari, Stéphanie Cottier, Fulvio Reggiori, Roger Schneiter*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
29 Downloads (Pure)

Abstract

Lipid droplets (LDs) are globular subcellular structures that store neutral lipids. LDs are closely associated with the endoplasmic reticulum (ER) and are limited by a phospholipid monolayer harboring a specific set of proteins. Most of these proteins associate with LDs through either an amphipathic helix or a membrane-embedded hairpin motif. Here, we address the question of whether integral membrane proteins can localize to the surface of LDs. To test this, we fused perilipin 3 (PLIN3), a mammalian LD-targeted protein, to ER-resident proteins. The resulting fusion proteins localized to the periphery of LDs in both yeast and mammalian cells. This peripheral LD localization of the fusion proteins, however, was due to a redistribution of the ER around LDs, as revealed by bimolecular fluorescence complementation between ER- and LD-localized partners. A LD-tethering function of PLIN3-containing membrane proteins was confirmed by fusing PLIN3 to the cytoplasmic domain of an outer mitochondrial membrane protein, OM14. Expression of OM14-PLIN3 induced a close apposition between LDs and mitochondria. These data indicate that the ER-LD junction constitutes a barrier for ER-resident integral membrane proteins.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalJournal of Cell Science
Volume135
Issue number5
Early online date2021
DOIs
Publication statusPublished - 1-Mar-2022

Keywords

  • Animals
  • Endoplasmic Reticulum/genetics
  • Lipid Droplets
  • Membrane Proteins/genetics
  • Phospholipids
  • Saccharomyces cerevisiae

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