Seipin regulates ER-lipid droplet contacts and cargo delivery

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http://hdl.handle.net/10138/173804

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Salo , V T , Belevich , I , Li , S , Karhinen , L , Vihinen , H , Vigouroux , C , Magre , J , Thiele , C , Hölttä-Vuori , M , Jokitalo , E & Ikonen , E 2016 , ' Seipin regulates ER-lipid droplet contacts and cargo delivery ' , EMBO Journal , vol. 35 , no. 24 , pp. 2699-2716 . https://doi.org/10.15252/embj.201695170

Title: Seipin regulates ER-lipid droplet contacts and cargo delivery
Author: Salo, Veijo T.; Belevich, Ilya; Li, Shiqian; Karhinen, Leena; Vihinen, Helena; Vigouroux, Corinne; Magre, Jocelyne; Thiele, Christoph; Hölttä-Vuori, Maarit; Jokitalo, Eija; Ikonen, Elina
Contributor: University of Helsinki, Medicum
University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
Date: 2016
Language: eng
Number of pages: 18
Belongs to series: EMBO Journal
ISSN: 0261-4189
URI: http://hdl.handle.net/10138/173804
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.
Subject: 1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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