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Identification of molecular machinery mediating ER to lipid droplet protein targeting

ABSTRACT: Lipid droplets (LDs) are organelles that store lipids and contain important metabolic proteins at their surfaces. The pathway for membrane-embedded hydrophobic proteins to reach the LD surface from the ER is largely unknown. Here, we find that many proteins, including key lipid synthesis and degradation enzymes, are excluded from forming LDs in the ER by the seipin oligomeric complex and target LDs via ER-LD membrane continuities that are established well after LD formation. We utilized systematic, unbiased approaches to identify key components of this ER-to-LD (ERTOLD) pathway. We find that specific membrane-fusion machinery, including membrane fusion regulators (Trs20 and Rab1), a tether (Rint1), and effectors (Syx5, membrin, Bet1, Ykt6), are required for late ERTOLD targeting of GPAT4 and other proteins that utilize this pathway. The fusion machinery components localize to the interface of LDs and the ER, and within the ER, appear to be organized at ER exit sites. Our data therefore uncover a novel mechanism for membrane protein trafficking for ERTOLD targeting via heterotypic organelle fusion between the ER and LDs.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Zon Weng Lai

LAB HEAD: Tobias Walther

PROVIDER: PXD027283 | Pride | 2022-06-27

REPOSITORIES: Pride

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