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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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			Action	DRS
	20200805_JS_S2LD01.raw	Raw
	20200805_JS_S2LD02.raw	Raw
	20200805_JS_S2LD03.raw	Raw
	20200805_JS_S2LD04.raw	Raw
	20200805_JS_S2LD05.raw	Raw

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Rab18 is not necessary for lipid droplet biogenesis or turnover in human mammary carcinoma cells

Project description:Rab GTPases recruit peripheral membrane proteins and can define organelle identity. Rab18 localizes to the ER but also to the surfaces of lipid droplets (LDs), where it has been implicated in effector protein recruitment and in defining LD identity. Here, we studied Rab18 localization and function in SUM159 cells. Rab18 localized to the ER and to LD membranes upon LD induction, with the latter depending on the Rab18 activation state. In cells lacking Rab18, LDs were modestly reduced in size and numbers, but we found little evidence for Rab18 function in LD formation, LD turnover upon cell starvation, or the targeting of several proteins to LDs. We conclude that Rab18 is not a general, necessary component of the protein machinery involved in LD biogenesis or turnover, but instead likely plays a specialized role in specific cell types

2018-06-06 | PXD009683 | Pride

The large GTPase Sey1/atlastin mediates lipid droplet- and FadL-dependent intracellular fatty acid metabolism of Legionella pneumophila

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Functional multi-organelle units control inflammatory lipid metabolism of macrophages

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Identification of a lipid droplet-plasma membrane tethering complex

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2022-06-09 | PXD022769 | Pride

Arabidopsis LDIP is an LDAP-interacting protein that influences lipid droplet biogenesis and neutral lipid homeostasis in both leaves and seeds

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