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A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion

Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear....

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Autores principales: Liu, Di-Ao, Tao, Kai, Wu, Bin, Yu, Ziyan, Szczepaniak, Malwina, Rames, Matthew, Yang, Changsong, Svitkina, Tatyana, Zhu, Yueyao, Xu, Fengyuan, Nan, Xiaolin, Guo, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613218/
https://www.ncbi.nlm.nih.gov/pubmed/37898620
http://dx.doi.org/10.1038/s41467-023-42661-0
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author Liu, Di-Ao
Tao, Kai
Wu, Bin
Yu, Ziyan
Szczepaniak, Malwina
Rames, Matthew
Yang, Changsong
Svitkina, Tatyana
Zhu, Yueyao
Xu, Fengyuan
Nan, Xiaolin
Guo, Wei
author_facet Liu, Di-Ao
Tao, Kai
Wu, Bin
Yu, Ziyan
Szczepaniak, Malwina
Rames, Matthew
Yang, Changsong
Svitkina, Tatyana
Zhu, Yueyao
Xu, Fengyuan
Nan, Xiaolin
Guo, Wei
author_sort Liu, Di-Ao
collection PubMed
description Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion.
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spelling pubmed-106132182023-10-30 A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion Liu, Di-Ao Tao, Kai Wu, Bin Yu, Ziyan Szczepaniak, Malwina Rames, Matthew Yang, Changsong Svitkina, Tatyana Zhu, Yueyao Xu, Fengyuan Nan, Xiaolin Guo, Wei Nat Commun Article Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion. Nature Publishing Group UK 2023-10-28 /pmc/articles/PMC10613218/ /pubmed/37898620 http://dx.doi.org/10.1038/s41467-023-42661-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Di-Ao
Tao, Kai
Wu, Bin
Yu, Ziyan
Szczepaniak, Malwina
Rames, Matthew
Yang, Changsong
Svitkina, Tatyana
Zhu, Yueyao
Xu, Fengyuan
Nan, Xiaolin
Guo, Wei
A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
title A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
title_full A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
title_fullStr A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
title_full_unstemmed A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
title_short A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
title_sort phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613218/
https://www.ncbi.nlm.nih.gov/pubmed/37898620
http://dx.doi.org/10.1038/s41467-023-42661-0
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