VPS13A and VPS13C Influence Lipid Droplet Abundance
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 (...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-09-01
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| Series: | Contact |
| Online Access: | https://doi.org/10.1177/25152564221125613 |
| _version_ | 1797833603158114304 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shuliang Chen |
| collection | DOAJ |
| description | 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 two lipid transfer proteins, VPS13A and VPS13C, in LD regulation. |
| first_indexed | 2024-04-09T14:26:52Z |
| format | Article |
| id | doaj.art-1e1a9db2ba5f434ba1ddfd7413e4ae42 |
| institution | Directory Open Access Journal |
| issn | 2515-2564 |
| language | English |
| last_indexed | 2024-04-09T14:26:52Z |
| publishDate | 2022-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Contact |
| spelling | doaj.art-1e1a9db2ba5f434ba1ddfd7413e4ae422023-05-04T03:33:19ZengSAGE PublishingContact2515-25642022-09-01510.1177/25152564221125613VPS13A and VPS13C Influence Lipid Droplet AbundanceShuliang Chen0Melissa A. Roberts1Chun-Yuan Chen2Sebastian Markmiller3Hong-Guang Wei4Gene W. Yeo5James G. Granneman6James A. Olzmann7Susan Ferro-Novick8 Department of Cellular and Molecular Medicine, , La Jolla, CA, USA Department of Nutritional Sciences and Toxicology, , CA, USA Department of Cellular and Molecular Medicine, , La Jolla, CA, USA Department of Cellular and Molecular Medicine, , La Jolla, CA, USA Center for Integrative Metabolic and Endocrine Research, , Detroit, MI, USA Department of Cellular and Molecular Medicine, , La Jolla, CA, USA Center for Integrative Metabolic and Endocrine Research, , Detroit, MI, USA Chan Zuckerberg Biohub, San Francisco, CA, USA Department of Cellular and Molecular Medicine, , La Jolla, CA, USALipid 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 two lipid transfer proteins, VPS13A and VPS13C, in LD regulation.https://doi.org/10.1177/25152564221125613 |
| spellingShingle | 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 VPS13A and VPS13C Influence Lipid Droplet Abundance Contact |
| title | VPS13A and VPS13C Influence Lipid Droplet Abundance |
| title_full | VPS13A and VPS13C Influence Lipid Droplet Abundance |
| title_fullStr | VPS13A and VPS13C Influence Lipid Droplet Abundance |
| title_full_unstemmed | VPS13A and VPS13C Influence Lipid Droplet Abundance |
| title_short | VPS13A and VPS13C Influence Lipid Droplet Abundance |
| title_sort | vps13a and vps13c influence lipid droplet abundance |
| url | https://doi.org/10.1177/25152564221125613 |
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