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Abstract
The glycolipid transfer protein (GLTP) has been linked to many cellular processes aside from its best-known in vitro function as a lipid transport protein. It has been proposed to act as a sensor and regulator of glycosphingolipid homeostasis in cells. Furthermore, through its previously determined interaction with the endoplasmic reticulum membrane protein VAP-A (vesicle-associated membrane protein-associated protein A), GLTP may also be involved in facilitating vesicular transport in cells. In this study, we characterized the phenotype of CRISPR/Cas9-mediated GLTP KO HeLa cells. We showed that motility, three-dimensional growth, and cellular metabolism were all altered by GLTP knockout. Expression of a GLTP mutant incapable of binding VAP disrupted cell spheroid formation, indicating that the GLTP–VAP interaction is linked to cellular adhesion, cohesion, and three-dimensional growth. Most notably, we found evidence that GLTP, through its interaction with VAP-A, affects vesicular trafficking, marking the first cellular process discovered to be directly impacted by a change in GLTP expression.
Original language | English |
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Article number | 104607 |
Number of pages | 17 |
Journal | Journal of Biological Chemistry |
Volume | 299 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2023 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Humans
- Biological Transport/genetics
- Carrier Proteins/genetics
- Cell Membrane/metabolism
- HeLa Cells
- Gene Knockout Techniques
- Protein Binding/genetics
- Gene Expression Regulation/genetics
- Cytosol/metabolism
- Cell Movement/genetics
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- 1 Finished
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The glycolipid transfer protein GLTP - A lipid sorting orchestrator in health and disease
Mattjus, P. (Principal Investigator)
01/09/19 → 31/05/24
Project: Foundation