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Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis
Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065113/ https://www.ncbi.nlm.nih.gov/pubmed/33893293 http://dx.doi.org/10.1038/s41467-021-22603-4 |
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author | Ferreira, Antonio P. A. Casamento, Alessandra Carrillo Roas, Sara Halff, Els F. Panambalana, James Subramaniam, Shaan Schützenhofer, Kira Chan Wah Hak, Laura McGourty, Kieran Thalassinos, Konstantinos Kittler, Josef T. Martinvalet, Denis Boucrot, Emmanuel |
author_facet | Ferreira, Antonio P. A. Casamento, Alessandra Carrillo Roas, Sara Halff, Els F. Panambalana, James Subramaniam, Shaan Schützenhofer, Kira Chan Wah Hak, Laura McGourty, Kieran Thalassinos, Konstantinos Kittler, Josef T. Martinvalet, Denis Boucrot, Emmanuel |
author_sort | Ferreira, Antonio P. A. |
collection | PubMed |
description | Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low. |
format | Online Article Text |
id | pubmed-8065113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80651132021-05-11 Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis Ferreira, Antonio P. A. Casamento, Alessandra Carrillo Roas, Sara Halff, Els F. Panambalana, James Subramaniam, Shaan Schützenhofer, Kira Chan Wah Hak, Laura McGourty, Kieran Thalassinos, Konstantinos Kittler, Josef T. Martinvalet, Denis Boucrot, Emmanuel Nat Commun Article Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low. Nature Publishing Group UK 2021-04-23 /pmc/articles/PMC8065113/ /pubmed/33893293 http://dx.doi.org/10.1038/s41467-021-22603-4 Text en © The Author(s) 2021 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ferreira, Antonio P. A. Casamento, Alessandra Carrillo Roas, Sara Halff, Els F. Panambalana, James Subramaniam, Shaan Schützenhofer, Kira Chan Wah Hak, Laura McGourty, Kieran Thalassinos, Konstantinos Kittler, Josef T. Martinvalet, Denis Boucrot, Emmanuel Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis |
title | Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis |
title_full | Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis |
title_fullStr | Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis |
title_full_unstemmed | Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis |
title_short | Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis |
title_sort | cdk5 and gsk3β inhibit fast endophilin-mediated endocytosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065113/ https://www.ncbi.nlm.nih.gov/pubmed/33893293 http://dx.doi.org/10.1038/s41467-021-22603-4 |
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