Seipin is required for converting nascent to mature lipid droplets

Huajin Wang; Michel Becuwe; Benjamin E. Housden; Chandramohan Chitraju; Ashley J. Porras; Morven M. Graham; Xinran N. Liu; Abdou Rachid Thiam; David B. Savage; Anil K. Agarwal; Abhimanyu Garg; Maria Jesus Olarte; Qingqing Lin; Florian Frohlich; Hans Kristian Hannibal-Bach; Srigokul Upadhyayula; Norbert Perrimon; Tomas Kirchhausen; Christer S. Ejsing; Tobias C. Walther; Robert V. Farese

doi:10.7554/eLife.16582

Seipin is required for converting nascent to mature lipid droplets

Huajin Wang, Michel Becuwe, Benjamin E. Housden, Chandramohan Chitraju, Ashley J. Porras, Morven M. Graham, Xinran N. Liu, Abdou Rachid Thiam, David B. Savage, Anil K. Agarwal, Abhimanyu Garg, Maria Jesus Olarte, Qingqing Lin, Florian Frohlich, Hans Kristian Hannibal-Bach, Srigokul Upadhyayula, Norbert Perrimon, Tomas Kirchhausen, Christer S. Ejsing, Tobias C. WaltherRobert V. Farese

Research output: Contribution to journal › Article › peer-review

217 Scopus citations

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.

Original language	English (US)
Article number	e16582
Journal	eLife
Volume	5
Issue number	AUGUST
DOIs	https://doi.org/10.7554/eLife.16582
State	Published - Aug 26 2016

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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10.7554/eLife.16582

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Wang, H., Becuwe, M., Housden, B. E., Chitraju, C., Porras, A. J., Graham, M. M., Liu, X. N., Thiam, A. R., Savage, D. B., Agarwal, A. K., Garg, A., Olarte, M. J., Lin, Q., Frohlich, F., Hannibal-Bach, H. K., Upadhyayula, S., Perrimon, N., Kirchhausen, T., Ejsing, C. S., ... Farese, R. V. (2016). Seipin is required for converting nascent to mature lipid droplets. eLife, 5(AUGUST), [e16582]. https://doi.org/10.7554/eLife.16582

Wang, H, Becuwe, M, Housden, BE, Chitraju, C, Porras, AJ, Graham, MM, Liu, XN, Thiam, AR, Savage, DB, Agarwal, AK , Garg, A, Olarte, MJ, Lin, Q, Frohlich, F, Hannibal-Bach, HK, Upadhyayula, S, Perrimon, N, Kirchhausen, T, Ejsing, CS, Walther, TC & Farese, RV 2016, 'Seipin is required for converting nascent to mature lipid droplets', eLife, vol. 5, no. AUGUST, e16582. https://doi.org/10.7554/eLife.16582

@article{0ae76c65ab8045efbe6e620e472d2a9d,

title = "Seipin is required for converting nascent to mature lipid droplets",

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.",

author = "Huajin Wang and Michel Becuwe and Housden, {Benjamin E.} and Chandramohan Chitraju and Porras, {Ashley J.} and Graham, {Morven M.} and Liu, {Xinran N.} and Thiam, {Abdou Rachid} and Savage, {David B.} and Agarwal, {Anil K.} and Abhimanyu Garg and Olarte, {Maria Jesus} and Qingqing Lin and Florian Frohlich and Hannibal-Bach, {Hans Kristian} and Srigokul Upadhyayula and Norbert Perrimon and Tomas Kirchhausen and Ejsing, {Christer S.} and Walther, {Tobias C.} and Farese, {Robert V.}",

note = "Funding Information: We thank Xun Huang (Chinese Academy of Sciences) for hSeipin cDNA, Stephanie Mohr of the Drosophila RNAi Screening Center at HMS (supported by NIH NIGMS R01 GM067761) and Gerry Mar-sischky of the HMS Genome Engineering Production Group (supported by the HMS Tools and Technology program) for reagents and advice, Zon Weng Lai, Manuele Piccolis, Zhihuan Li, and Nora Kory (Harvard T H Chan School of Public Health) for their help with experiments and discussions, Guangwei Du (University of Texas Health Science Center) for providing the GFP-PASS plasmid, Jan Hoffmann (Carnegie Mellon University) for help with ER morphology evaluation, and Gary Howard for editorial assistance. Canadian Institutes of Health Research Fellowship Award Huajin Wang European Molecular Biology Organization Longterm Fellowship EMBOLFT355 Michel Becuwe Wellcome Trust WT107064 David B Savage NIHR Cambridge Biomedical Research Centre David B Savage, Howard Hughes Medical Institute Norbert Perrimon Tobias C Walther Biogen Tomas Kirchhausen National Institutes of Health GM-075252 Tomas Kirchhausen Villum Fonden VKR023439 Christer S Ejsing Strategiske Forskningsr{\aa}d 11-116196 Christer S Ejsing National Institutes of Health GM097194 Tobias C Walther G Harold and Leila Y. Mathers Foundation Tobias C Walther National Institutes of Health GM099844 Robert V Farese Jr. Publisher Copyright: {\textcopyright} Wang et al.",

year = "2016",

month = aug,

day = "26",

doi = "10.7554/eLife.16582",

language = "English (US)",

volume = "5",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

number = "AUGUST",

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TY - JOUR

T1 - Seipin is required for converting nascent to mature lipid droplets

AU - Wang, Huajin

AU - Becuwe, Michel

AU - Housden, Benjamin E.

AU - Chitraju, Chandramohan

AU - Porras, Ashley J.

AU - Graham, Morven M.

AU - Liu, Xinran N.

AU - Thiam, Abdou Rachid

AU - Savage, David B.

AU - Agarwal, Anil K.

AU - Garg, Abhimanyu

AU - Olarte, Maria Jesus

AU - Lin, Qingqing

AU - Frohlich, Florian

AU - Hannibal-Bach, Hans Kristian

AU - Upadhyayula, Srigokul

AU - Perrimon, Norbert

AU - Kirchhausen, Tomas

AU - Ejsing, Christer S.

AU - Walther, Tobias C.

AU - Farese, Robert V.

N1 - Funding Information: We thank Xun Huang (Chinese Academy of Sciences) for hSeipin cDNA, Stephanie Mohr of the Drosophila RNAi Screening Center at HMS (supported by NIH NIGMS R01 GM067761) and Gerry Mar-sischky of the HMS Genome Engineering Production Group (supported by the HMS Tools and Technology program) for reagents and advice, Zon Weng Lai, Manuele Piccolis, Zhihuan Li, and Nora Kory (Harvard T H Chan School of Public Health) for their help with experiments and discussions, Guangwei Du (University of Texas Health Science Center) for providing the GFP-PASS plasmid, Jan Hoffmann (Carnegie Mellon University) for help with ER morphology evaluation, and Gary Howard for editorial assistance. Canadian Institutes of Health Research Fellowship Award Huajin Wang European Molecular Biology Organization Longterm Fellowship EMBOLFT355 Michel Becuwe Wellcome Trust WT107064 David B Savage NIHR Cambridge Biomedical Research Centre David B Savage, Howard Hughes Medical Institute Norbert Perrimon Tobias C Walther Biogen Tomas Kirchhausen National Institutes of Health GM-075252 Tomas Kirchhausen Villum Fonden VKR023439 Christer S Ejsing Strategiske Forskningsråd 11-116196 Christer S Ejsing National Institutes of Health GM097194 Tobias C Walther G Harold and Leila Y. Mathers Foundation Tobias C Walther National Institutes of Health GM099844 Robert V Farese Jr. Publisher Copyright: © Wang et al.

PY - 2016/8/26

Y1 - 2016/8/26

N2 - 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.

AB - 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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U2 - 10.7554/eLife.16582

DO - 10.7554/eLife.16582

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VL - 5

JO - eLife

JF - eLife

IS - AUGUST

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ER -

Seipin is required for converting nascent to mature lipid droplets

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