Seipin is required for converting nascent to mature lipid droplets
- Carnegie Mellon University, United States
- Harvard T. H. Chan School of Public Health, United States
- Harvard Medical School, United States
- Yale School of Medicine, United States
- PSL Research University, France
- The University of Cambridge Metabolic Research Laboratories, United Kingdom
- UT Southwestern Medical Center, United States
- University of Southern Denmark, Denmark
Abstract
How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.
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Funding
National Institutes of Health (GM099844, GM097194, GM-075252)
- Tomas Kirchhausen
- Tobias C Walther
- Robert V Farese
Howard Hughes Medical Institute
- Norbert Perrimon
- Tobias C Walther
G Harold and Leila Y. Mathers Foundation
- Tobias C Walther
Villum Fonden (VKR023439)
- Christer S Ejsing
Danish Council for Strategic Research (11-116196)
- Christer S Ejsing
Wellcome Trust (WT107064)
- David B Savage
Cambridge NIHR BRC
- David B Savage
Biogen
- Tomas Kirchhausen
Canadian Institutes of Health Research (Fellowship Award)
- Huajin Wang
European Molecular Biology Organization (Longterm Fellowship EMBOLFT355)
- Michel Becuwe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Seipin is required for converting nascent to mature lipid droplets
eLife 5:e16582.
https://doi.org/10.7554/eLife.16582
