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WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms
Autophagosome formation requires PROPPIN/WIPI proteins and monophosphorylated phosphoinositides, such as phosphatidylinositol-3-phosphate (PtdIns3P) or PtdIns5P. This process occurs in association with mammalian endosomes, where the PROPPIN WIPI1 has additional, undefined roles in vesicular traffic....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632285/ https://www.ncbi.nlm.nih.gov/pubmed/33685363 http://dx.doi.org/10.1080/15548627.2021.1886830 |
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author | De Leo, Maria Giovanna Berger, Philipp Mayer, Andreas |
author_facet | De Leo, Maria Giovanna Berger, Philipp Mayer, Andreas |
author_sort | De Leo, Maria Giovanna |
collection | PubMed |
description | Autophagosome formation requires PROPPIN/WIPI proteins and monophosphorylated phosphoinositides, such as phosphatidylinositol-3-phosphate (PtdIns3P) or PtdIns5P. This process occurs in association with mammalian endosomes, where the PROPPIN WIPI1 has additional, undefined roles in vesicular traffic. To explore whether these functions are interconnected, we dissected routes and subreactions of endosomal trafficking requiring WIPI1. WIPI1 specifically acts in the formation and fission of tubulo-vesicular endosomal transport carriers. This activity supports the PtdIns(3,5)P(2)-dependent transport of endosomal cargo toward the plasma membrane, Golgi, and lysosomes, suggesting a general role of WIPI1 in endosomal protein exit. Three features differentiate the endosomal and macroautophagic/autophagic activities of WIPI1: phosphoinositide binding site II, the requirement for PtdIns(3,5)P(2), and bilayer deformation through a conserved amphipathic α-helix. Their inactivation preserves autophagy but leads to a strong enlargement of endosomes, which accumulate micrometer-long endosomal membrane tubules carrying cargo proteins. WIPI1 thus supports autophagy and protein exit from endosomes by different modes of action. We propose that the type of phosphoinositides occupying its two lipid binding sites, the most unusual feature of PROPPIN/WIPI family proteins, switches between these effector functions. Abbreviations: EGF: epidermal growth factorEGFR: epidermal growth factor receptorKD: knockdownKO: knockoutPtdIns3P: phosphatidylinositol-3-phosphatePtdIns5P: phosphatidylinositol-5-phosphatePtdIns(3,5)P(2): phosphatidylinositol-3,5-bisphosphateTF: transferrinTFRC: transferrin receptorWT: wildtype |
format | Online Article Text |
id | pubmed-8632285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-86322852021-12-01 WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms De Leo, Maria Giovanna Berger, Philipp Mayer, Andreas Autophagy Research Paper Autophagosome formation requires PROPPIN/WIPI proteins and monophosphorylated phosphoinositides, such as phosphatidylinositol-3-phosphate (PtdIns3P) or PtdIns5P. This process occurs in association with mammalian endosomes, where the PROPPIN WIPI1 has additional, undefined roles in vesicular traffic. To explore whether these functions are interconnected, we dissected routes and subreactions of endosomal trafficking requiring WIPI1. WIPI1 specifically acts in the formation and fission of tubulo-vesicular endosomal transport carriers. This activity supports the PtdIns(3,5)P(2)-dependent transport of endosomal cargo toward the plasma membrane, Golgi, and lysosomes, suggesting a general role of WIPI1 in endosomal protein exit. Three features differentiate the endosomal and macroautophagic/autophagic activities of WIPI1: phosphoinositide binding site II, the requirement for PtdIns(3,5)P(2), and bilayer deformation through a conserved amphipathic α-helix. Their inactivation preserves autophagy but leads to a strong enlargement of endosomes, which accumulate micrometer-long endosomal membrane tubules carrying cargo proteins. WIPI1 thus supports autophagy and protein exit from endosomes by different modes of action. We propose that the type of phosphoinositides occupying its two lipid binding sites, the most unusual feature of PROPPIN/WIPI family proteins, switches between these effector functions. Abbreviations: EGF: epidermal growth factorEGFR: epidermal growth factor receptorKD: knockdownKO: knockoutPtdIns3P: phosphatidylinositol-3-phosphatePtdIns5P: phosphatidylinositol-5-phosphatePtdIns(3,5)P(2): phosphatidylinositol-3,5-bisphosphateTF: transferrinTFRC: transferrin receptorWT: wildtype Taylor & Francis 2021-03-08 /pmc/articles/PMC8632285/ /pubmed/33685363 http://dx.doi.org/10.1080/15548627.2021.1886830 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Paper De Leo, Maria Giovanna Berger, Philipp Mayer, Andreas WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
title | WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
title_full | WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
title_fullStr | WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
title_full_unstemmed | WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
title_short | WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
title_sort | wipi1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632285/ https://www.ncbi.nlm.nih.gov/pubmed/33685363 http://dx.doi.org/10.1080/15548627.2021.1886830 |
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