Lipid droplet membrane proteins ubiquitylation
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Rattus Norvegicus (rat)
SUBMITTER: 
Paul Thomes
LAB HEAD: Paul Thomes
PROVIDER: PXD038662 | Pride | 2023-02-27
REPOSITORIES: Pride
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Project description:Lipid droplet (LD) function is regulated by a complement of integral and peripheral proteins that associate with the 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 U2OS and Huh7 cells identified the vast majority of previously validated LD proteins, excluded common contaminating proteins, and revealed new LD proteins.
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Project description:Multilocular adipocytes are a hallmark of thermogenic adipose tissue, but the factors that enforce this cellular phenotype are unknown. Here, we show that an adipocyte-specific product of the Clstn3 locus (CLSTN3b) present only in placental mammals facilitates the rapid utilization of stored triglyceride by limiting lipid droplet (LD) size. CLSTN3b is an integral ER protein that localizes to ER-LD contact sites via a conserved hairpin domain. Mice lacking CLSTN3b have altered LD morphology and increased lipid accumulation in BAT, as well as heightened sensitivity to cold challenge, despite having no defect in adrenergic signaling. Conversely, forced expression of CLSTN3b promotes a multilocular LD phenotype in cultured cells and BAT and facilitates triglyceride utilization. Mechanistically, CLSTN3b associates with CIDE proteins and impairs their ability to transfer lipid between droplets, thereby limiting LD expansion. These findings define a molecular mechanism that maximizes LD surface area to facilitate lipid utilization in thermogenic adipocytes.
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