Seipin regulates ER-lipid droplet contacts and cargo delivery

Veijo T. Salo, Ilya Belevich, Shiqian Li, Leena Karhinen, Helena Vihinen, Corinne Vigouroux, Jocelyne Magre, Christoph Thiele, Maarit Hölttä-Vuori, Eija Jokitalo, Elina Ikonen

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
JournalEMBO Journal
Volume35
Issue number24
Pages (from-to)2699-2716
Number of pages18
ISSN0261-4189
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • 3111 Biomedicine

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