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Seipin regulates ER–lipid droplet contacts and cargo delivery

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...

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Autores principales: Salo, Veijo T, Belevich, Ilya, Li, Shiqian, Karhinen, Leena, Vihinen, Helena, Vigouroux, Corinne, Magré, Jocelyne, Thiele, Christoph, Hölttä‐Vuori, Maarit, Jokitalo, Eija, Ikonen, Elina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167346/
https://www.ncbi.nlm.nih.gov/pubmed/27879284
http://dx.doi.org/10.15252/embj.201695170
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author Salo, Veijo T
Belevich, Ilya
Li, Shiqian
Karhinen, Leena
Vihinen, Helena
Vigouroux, Corinne
Magré, Jocelyne
Thiele, Christoph
Hölttä‐Vuori, Maarit
Jokitalo, Eija
Ikonen, Elina
author_facet Salo, Veijo T
Belevich, Ilya
Li, Shiqian
Karhinen, Leena
Vihinen, Helena
Vigouroux, Corinne
Magré, Jocelyne
Thiele, Christoph
Hölttä‐Vuori, Maarit
Jokitalo, Eija
Ikonen, Elina
author_sort Salo, Veijo T
collection PubMed
description 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.
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spelling pubmed-51673462016-12-28 Seipin regulates ER–lipid droplet contacts and cargo delivery Salo, Veijo T Belevich, Ilya Li, Shiqian Karhinen, Leena Vihinen, Helena Vigouroux, Corinne Magré, Jocelyne Thiele, Christoph Hölttä‐Vuori, Maarit Jokitalo, Eija Ikonen, Elina EMBO J Articles 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. John Wiley and Sons Inc. 2016-11-22 2016-12-15 /pmc/articles/PMC5167346/ /pubmed/27879284 http://dx.doi.org/10.15252/embj.201695170 Text en © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Salo, Veijo T
Belevich, Ilya
Li, Shiqian
Karhinen, Leena
Vihinen, Helena
Vigouroux, Corinne
Magré, Jocelyne
Thiele, Christoph
Hölttä‐Vuori, Maarit
Jokitalo, Eija
Ikonen, Elina
Seipin regulates ER–lipid droplet contacts and cargo delivery
title Seipin regulates ER–lipid droplet contacts and cargo delivery
title_full Seipin regulates ER–lipid droplet contacts and cargo delivery
title_fullStr Seipin regulates ER–lipid droplet contacts and cargo delivery
title_full_unstemmed Seipin regulates ER–lipid droplet contacts and cargo delivery
title_short Seipin regulates ER–lipid droplet contacts and cargo delivery
title_sort seipin regulates er–lipid droplet contacts and cargo delivery
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167346/
https://www.ncbi.nlm.nih.gov/pubmed/27879284
http://dx.doi.org/10.15252/embj.201695170
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