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Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane

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...

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Autores principales: Nurmi, Henrik, Backman, Anders P.E., Halin, Josefin, Lönnfors, Max, Blom, Tomas, Roos-Mattjus, Pia, Mattjus, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140181/
https://www.ncbi.nlm.nih.gov/pubmed/36924944
http://dx.doi.org/10.1016/j.jbc.2023.104607
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author Nurmi, Henrik
Backman, Anders P.E.
Halin, Josefin
Lönnfors, Max
Blom, Tomas
Roos-Mattjus, Pia
Mattjus, Peter
author_facet Nurmi, Henrik
Backman, Anders P.E.
Halin, Josefin
Lönnfors, Max
Blom, Tomas
Roos-Mattjus, Pia
Mattjus, Peter
author_sort Nurmi, Henrik
collection PubMed
description 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.
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spelling pubmed-101401812023-04-29 Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane Nurmi, Henrik Backman, Anders P.E. Halin, Josefin Lönnfors, Max Blom, Tomas Roos-Mattjus, Pia Mattjus, Peter J Biol Chem Research Article 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. American Society for Biochemistry and Molecular Biology 2023-03-15 /pmc/articles/PMC10140181/ /pubmed/36924944 http://dx.doi.org/10.1016/j.jbc.2023.104607 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Nurmi, Henrik
Backman, Anders P.E.
Halin, Josefin
Lönnfors, Max
Blom, Tomas
Roos-Mattjus, Pia
Mattjus, Peter
Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
title Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
title_full Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
title_fullStr Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
title_full_unstemmed Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
title_short Glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
title_sort glycolipid transfer protein knockout disrupts vesicle trafficking to the plasma membrane
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140181/
https://www.ncbi.nlm.nih.gov/pubmed/36924944
http://dx.doi.org/10.1016/j.jbc.2023.104607
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