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EMBO J. 2016 Dec 15;35(24):2699-2716. Epub 2016 Nov 22.

Seipin regulates ER-lipid droplet contacts and cargo delivery.

Author information

1
Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
2
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
3
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
4
Sorbonne Universités, UPMC Univ Paris 6, Inserm UMR_S938, Saint-Antoine Research Center, Institute of Cardiometabolism And Nutrition, AP-HP, Saint-Antoine Hospital Department of Molecular Biology and Genetics, Paris, France.
5
l'Institut du Thorax, INSERM CNRS UNIV Nantes, Nantes, France.
6
LIMES Institute, Bonn University, Bonn, Germany.
7
Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland elina.ikonen@helsinki.fi.

Abstract

Seipin is an endoplasmic reticulum (ER) membrane protein implicated in lipid droplet (LD) biogenesis and mutated in severe congenital lipodystrophy (BSCL2). Here, we show that seipin is stably associated with nascent ER-LD contacts in human cells, typically via one mobile focal point per LD Seipin appears critical for such contacts since ER-LD contacts were completely missing or morphologically aberrant in seipin knockout and BSCL2 patient cells. In parallel, LD mobility was increased and protein delivery from the ER to LDs to promote LD growth was decreased. Moreover, while growing LDs normally acquire lipid and protein constituents from the ER, this process was compromised in seipin-deficient cells. In the absence of seipin, the initial synthesis of neutral lipids from exogenous fatty acid was normal, but fatty acid incorporation into neutral lipids in cells with pre-existing LDs was impaired. Together, our data suggest that seipin helps to connect newly formed LDs to the ER and that by stabilizing ER-LD contacts seipin facilitates the incorporation of protein and lipid cargo into growing LDs in human cells.

KEYWORDS:

electron microscopy; lipid storage; lipodystrophy; membrane contact sites

PMID:
27879284
PMCID:
PMC5167346
DOI:
10.15252/embj.201695170
[Indexed for MEDLINE]
Free PMC Article

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