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Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles

The formation of extracellular vesicles (EVs) is induced by the sphingolipid ceramide. How this pathway is regulated is not entirely understood. Here, we report that the ceramide transport protein (CERT) mediates a non‐vesicular transport of ceramide between the endoplasmic reticulum (ER) and the mu...

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Autores principales: Crivelli, Simone M., Giovagnoni, Caterina, Zhu, Zhihui, Tripathi, Priyanka, Elsherbini, Ahmed, Quadri, Zainuddin, Pu, Jian, Zhang, Liping, Ferko, Branislav, Berkes, Dusan, Spassieva, Stefka D., Martinez‐Martinez, Pilar, Bieberich, Erhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156972/
https://www.ncbi.nlm.nih.gov/pubmed/35642450
http://dx.doi.org/10.1002/jev2.12233
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author Crivelli, Simone M.
Giovagnoni, Caterina
Zhu, Zhihui
Tripathi, Priyanka
Elsherbini, Ahmed
Quadri, Zainuddin
Pu, Jian
Zhang, Liping
Ferko, Branislav
Berkes, Dusan
Spassieva, Stefka D.
Martinez‐Martinez, Pilar
Bieberich, Erhard
author_facet Crivelli, Simone M.
Giovagnoni, Caterina
Zhu, Zhihui
Tripathi, Priyanka
Elsherbini, Ahmed
Quadri, Zainuddin
Pu, Jian
Zhang, Liping
Ferko, Branislav
Berkes, Dusan
Spassieva, Stefka D.
Martinez‐Martinez, Pilar
Bieberich, Erhard
author_sort Crivelli, Simone M.
collection PubMed
description The formation of extracellular vesicles (EVs) is induced by the sphingolipid ceramide. How this pathway is regulated is not entirely understood. Here, we report that the ceramide transport protein (CERT) mediates a non‐vesicular transport of ceramide between the endoplasmic reticulum (ER) and the multivesicular endosome at contact sites. The process depends on the interaction of CERT's PH domain with PI4P generated by PI4KIIα at endosomes. Furthermore, a complex is formed between the START domain of CERT, which carries ceramide, and the Tsg101 protein, which is part of the endosomal sorting complex required for transport (ESCRT‐I). Inhibition of ceramide biosynthesis reduces CERT‐Tsg101 complex formation. Overexpression of CERT increases EV secretion while its inhibition reduces EV formation and the concentration of ceramides and sphingomyelins in EVs. In conclusion, we discovered a function of CERT in regulating the sphingolipid composition and biogenesis of EVs, which links ceramide to the ESCRT‐dependent pathway.
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spelling pubmed-91569722022-06-04 Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles Crivelli, Simone M. Giovagnoni, Caterina Zhu, Zhihui Tripathi, Priyanka Elsherbini, Ahmed Quadri, Zainuddin Pu, Jian Zhang, Liping Ferko, Branislav Berkes, Dusan Spassieva, Stefka D. Martinez‐Martinez, Pilar Bieberich, Erhard J Extracell Vesicles Research Articles The formation of extracellular vesicles (EVs) is induced by the sphingolipid ceramide. How this pathway is regulated is not entirely understood. Here, we report that the ceramide transport protein (CERT) mediates a non‐vesicular transport of ceramide between the endoplasmic reticulum (ER) and the multivesicular endosome at contact sites. The process depends on the interaction of CERT's PH domain with PI4P generated by PI4KIIα at endosomes. Furthermore, a complex is formed between the START domain of CERT, which carries ceramide, and the Tsg101 protein, which is part of the endosomal sorting complex required for transport (ESCRT‐I). Inhibition of ceramide biosynthesis reduces CERT‐Tsg101 complex formation. Overexpression of CERT increases EV secretion while its inhibition reduces EV formation and the concentration of ceramides and sphingomyelins in EVs. In conclusion, we discovered a function of CERT in regulating the sphingolipid composition and biogenesis of EVs, which links ceramide to the ESCRT‐dependent pathway. John Wiley and Sons Inc. 2022-06-01 2022-06 /pmc/articles/PMC9156972/ /pubmed/35642450 http://dx.doi.org/10.1002/jev2.12233 Text en © 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Crivelli, Simone M.
Giovagnoni, Caterina
Zhu, Zhihui
Tripathi, Priyanka
Elsherbini, Ahmed
Quadri, Zainuddin
Pu, Jian
Zhang, Liping
Ferko, Branislav
Berkes, Dusan
Spassieva, Stefka D.
Martinez‐Martinez, Pilar
Bieberich, Erhard
Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
title Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
title_full Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
title_fullStr Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
title_full_unstemmed Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
title_short Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
title_sort function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156972/
https://www.ncbi.nlm.nih.gov/pubmed/35642450
http://dx.doi.org/10.1002/jev2.12233
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