Identification of two pathways mediating protein targeting from ER to lipid droplets
Journal
Nature Cell Biology
Journal Volume
24
Journal Issue
9
Pages
1364–1377
Date Issued
2022-09-01
Author(s)
Jiunn Song
Arda Mizrak
Marcelo Cicconet
Zon Weng Lai
Wei-Chun Tang
Chieh-Han Lu
Stephanie E. Mohr
Robert V. Farese, Jr.
Tobias C. Walther
Abstract
Pathways localizing proteins to their sites of action are essential for eukaryotic cell organization and function. Although mechanisms of protein targeting to many organelles have been defined, how proteins, such as metabolic enzymes, target from the endoplasmic reticulum (ER) to cellular lipid droplets (LDs) is poorly understood. Here we identify two distinct pathways for ER-to-LD protein targeting: early targeting at LD formation sites during formation, and late targeting to mature LDs after their formation. Using systematic, unbiased approaches in Drosophila cells, we identified specific membrane-fusion machinery, including regulators, a tether and SNARE proteins, that are required for the late targeting pathway. Components of this fusion machinery localize to LD-ER interfaces and organize at ER exit sites. We identified multiple cargoes for early and late ER-to-LD targeting pathways. Our findings provide a model for how proteins target to LDs from the ER either during LD formation or by protein-catalysed formation of membrane bridges.
SDGs
Publisher
Springer Nature
Type
journal article