Seipin regulates ER-lipid droplet contacts and cargo delivery

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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.
Alkuperäiskielienglanti
LehtiEMBO Journal
Vuosikerta35
Numero24
Sivut2699-2716
Sivumäärä18
ISSN0261-4189
DOI - pysyväislinkit
TilaJulkaistu - 2016
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 1182 Biokemia, solu- ja molekyylibiologia
  • 3111 Biolääketieteet

Lainaa tätä

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title = "Seipin regulates ER-lipid droplet contacts and cargo delivery",
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 = "1182 Biochemistry, cell and molecular biology, 3111 Biomedicine",
author = "Salo, {Veijo T.} and Ilya Belevich and Shiqian Li and Leena Karhinen and Helena Vihinen and Corinne Vigouroux and Jocelyne Magre and Christoph Thiele and Maarit H{\"o}ltt{\"a}-Vuori and Eija Jokitalo and Elina Ikonen",
year = "2016",
doi = "10.15252/embj.201695170",
language = "English",
volume = "35",
pages = "2699--2716",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley",
number = "24",

}

Seipin regulates ER-lipid droplet contacts and cargo delivery. / Salo, Veijo T.; Belevich, Ilya; Li, Shiqian; Karhinen, Leena; Vihinen, Helena; Vigouroux, Corinne; Magre, Jocelyne; Thiele, Christoph; Hölttä-Vuori, Maarit; Jokitalo, Eija; Ikonen, Elina.

julkaisussa: EMBO Journal, Vuosikerta 35, Nro 24, 2016, s. 2699-2716.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Seipin regulates ER-lipid droplet contacts and cargo delivery

AU - Salo, Veijo T.

AU - Belevich, Ilya

AU - Li, Shiqian

AU - Karhinen, Leena

AU - Vihinen, Helena

AU - Vigouroux, Corinne

AU - Magre, Jocelyne

AU - Thiele, Christoph

AU - Hölttä-Vuori, Maarit

AU - Jokitalo, Eija

AU - Ikonen, Elina

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - 1182 Biochemistry, cell and molecular biology

KW - 3111 Biomedicine

U2 - 10.15252/embj.201695170

DO - 10.15252/embj.201695170

M3 - Article

VL - 35

SP - 2699

EP - 2716

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 24

ER -