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VPS13A and VPS13C influence lipid droplet abundance

Shuliang Chen, Melissa A. Roberts, Chun-Yuan Chen, Sebastian Markmiller, Hong-Guang Wei, Gene W. Yeo, James G Granneman, View ORCID ProfileJames A. Olzmann, Susan Ferro-Novick
doi: https://doi.org/10.1101/2022.06.21.497109
Shuliang Chen
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
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Melissa A. Roberts
2Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
3Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
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Chun-Yuan Chen
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
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Sebastian Markmiller
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
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Hong-Guang Wei
4Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI, 48201, USA
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Gene W. Yeo
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
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James G Granneman
4Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI, 48201, USA
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James A. Olzmann
2Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
3Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA
5Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
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  • ORCID record for James A. Olzmann
  • For correspondence: sferronovick@health.ucsd.edu olzmann@berkeley.edu
Susan Ferro-Novick
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
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  • For correspondence: sferronovick@health.ucsd.edu olzmann@berkeley.edu
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Abstract

Lipid transfer proteins mediate the exchange of lipids between closely apposed membranes at organelle contact sites and play key roles in lipid metabolism, membrane homeostasis, and cellular signaling. A recently discovered novel family of lipid transfer proteins, which includes the VPS13 proteins (VPS13A-D), adopt a rod-like bridge conformation with an extended hydrophobic groove that enables the bulk transfer of membrane lipids for membrane growth. Loss of function mutations in VPS13A and VPS13C cause chorea acanthocytosis and Parkinson's disease, respectively. VPS13A and VPS13C localize to multiple organelle contact sites, including endoplasmic reticulum (ER) - lipid droplet (LD) contact sites, but the functional roles of these proteins in LD regulation remains mostly unexplored. Here, we employ CRISPR-Cas9 genome editing to generate VPS13A and VPS13C knockout cell lines in U-2 OS cells via deletion of exon 2 and introduction of an early frameshift. Analysis of LD content in these cell lines revealed that loss of either VPS13A or VPS13C results in reduced LD abundance under oleate-stimulated conditions. These data implicate VPS13A and VPS13C in LD regulation and raise the intriguing possibility that VPS13A and VPS13C-mediated lipid transfer facilitates LD biogenesis.

Competing Interest Statement

J.A.O. is a member of the scientific advisory board for Vicinitas Therapeutics. G.W.Y. is a co-founder, member of the board of directors, equity holder, and paid consultant for Locanabio and Eclipse Bioinnovations. G.W.Y. is a Distinguished Visiting Professor at the National University of Singapore. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The authors declare no other competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 23, 2022.
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VPS13A and VPS13C influence lipid droplet abundance
Shuliang Chen, Melissa A. Roberts, Chun-Yuan Chen, Sebastian Markmiller, Hong-Guang Wei, Gene W. Yeo, James G Granneman, James A. Olzmann, Susan Ferro-Novick
bioRxiv 2022.06.21.497109; doi: https://doi.org/10.1101/2022.06.21.497109
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VPS13A and VPS13C influence lipid droplet abundance
Shuliang Chen, Melissa A. Roberts, Chun-Yuan Chen, Sebastian Markmiller, Hong-Guang Wei, Gene W. Yeo, James G Granneman, James A. Olzmann, Susan Ferro-Novick
bioRxiv 2022.06.21.497109; doi: https://doi.org/10.1101/2022.06.21.497109

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