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Seipin regulates ER –lipid droplet contacts and cargo delivery
Author(s) -
Salo Veijo T,
Belevich Ilya,
Li Shiqian,
Karhinen Leena,
Vihinen Helena,
Vigouroux Corinne,
Magré Jocelyne,
Thiele Christoph,
HölttäVuori Maarit,
Jokitalo Eija,
Ikonen Elina
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695170
Subject(s) - endoplasmic reticulum , lipid droplet , biology , unfolded protein response , lipid metabolism , microbiology and biotechnology , biochemistry
Seipin is an endoplasmic reticulum ( ER ) membrane protein implicated in lipid droplet ( LD ) biogenesis and mutated in severe congenital lipodystrophy ( BSCL 2). 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 BSCL 2 patient cells. In parallel, LD mobility was increased and protein delivery from the ER to LD s to promote LD growth was decreased. Moreover, while growing LD s 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 LD s was impaired. Together, our data suggest that seipin helps to connect newly formed LD s to the ER and that by stabilizing ER – LD contacts seipin facilitates the incorporation of protein and lipid cargo into growing LD s in human cells.