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De novo formation of early endosomes during Rab5-to-Rab7a transition

Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch, where Rab5 is gradually exchanged by Rab7a on the same endosom...

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Autores principales: Skjeldal, Frode Miltzow, Haugen, Linda Hofstad, Mateus, Duarte, Frei, Dominik M., Rødseth, Anna Vik, Hu, Xian, Bakke, Oddmund
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106955/
https://www.ncbi.nlm.nih.gov/pubmed/33737317
http://dx.doi.org/10.1242/jcs.254185
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author Skjeldal, Frode Miltzow
Haugen, Linda Hofstad
Mateus, Duarte
Frei, Dominik M.
Rødseth, Anna Vik
Hu, Xian
Bakke, Oddmund
author_facet Skjeldal, Frode Miltzow
Haugen, Linda Hofstad
Mateus, Duarte
Frei, Dominik M.
Rødseth, Anna Vik
Hu, Xian
Bakke, Oddmund
author_sort Skjeldal, Frode Miltzow
collection PubMed
description Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch, where Rab5 is gradually exchanged by Rab7a on the same endosome. Here, we provide new insight into the mechanism of endosomal maturation, for which we have discovered a stepwise Rab5 detachment, sequentially regulated by Rab7a. The initial detachment of Rab5 is Rab7a independent and demonstrates a diffusion-like first-phase exchange between the cytosol and the endosomal membrane, and a second phase, in which Rab5 converges into specific domains that detach as a Rab5 indigenous endosome. Consequently, we show that early endosomal maturation regulated through the Rab5-to-Rab7a switch induces the formation of new fully functional Rab5-positive early endosomes. Progression through stepwise early endosomal maturation regulates the direction of transport and, concomitantly, the homeostasis of early endosomes.
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spelling pubmed-81069552021-05-11 De novo formation of early endosomes during Rab5-to-Rab7a transition Skjeldal, Frode Miltzow Haugen, Linda Hofstad Mateus, Duarte Frei, Dominik M. Rødseth, Anna Vik Hu, Xian Bakke, Oddmund J Cell Sci Research Article Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch, where Rab5 is gradually exchanged by Rab7a on the same endosome. Here, we provide new insight into the mechanism of endosomal maturation, for which we have discovered a stepwise Rab5 detachment, sequentially regulated by Rab7a. The initial detachment of Rab5 is Rab7a independent and demonstrates a diffusion-like first-phase exchange between the cytosol and the endosomal membrane, and a second phase, in which Rab5 converges into specific domains that detach as a Rab5 indigenous endosome. Consequently, we show that early endosomal maturation regulated through the Rab5-to-Rab7a switch induces the formation of new fully functional Rab5-positive early endosomes. Progression through stepwise early endosomal maturation regulates the direction of transport and, concomitantly, the homeostasis of early endosomes. The Company of Biologists Ltd 2021-04-27 /pmc/articles/PMC8106955/ /pubmed/33737317 http://dx.doi.org/10.1242/jcs.254185 Text en © 2021. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Skjeldal, Frode Miltzow
Haugen, Linda Hofstad
Mateus, Duarte
Frei, Dominik M.
Rødseth, Anna Vik
Hu, Xian
Bakke, Oddmund
De novo formation of early endosomes during Rab5-to-Rab7a transition
title De novo formation of early endosomes during Rab5-to-Rab7a transition
title_full De novo formation of early endosomes during Rab5-to-Rab7a transition
title_fullStr De novo formation of early endosomes during Rab5-to-Rab7a transition
title_full_unstemmed De novo formation of early endosomes during Rab5-to-Rab7a transition
title_short De novo formation of early endosomes during Rab5-to-Rab7a transition
title_sort de novo formation of early endosomes during rab5-to-rab7a transition
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106955/
https://www.ncbi.nlm.nih.gov/pubmed/33737317
http://dx.doi.org/10.1242/jcs.254185
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