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Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes
Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion and migration, as well as failure to undergo epidermal to mesenchymal transition. However, the primary molecular role of kazrin, which might contri...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181827/ https://www.ncbi.nlm.nih.gov/pubmed/37096882 http://dx.doi.org/10.7554/eLife.83793 |
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author | Hernandez-Perez, Ines Rubio, Javier Baumann, Adrian Girao, Henrique Ferrando, Miriam Rebollo, Elena Aragay, Anna M Geli, María Isabel |
author_facet | Hernandez-Perez, Ines Rubio, Javier Baumann, Adrian Girao, Henrique Ferrando, Miriam Rebollo, Elena Aragay, Anna M Geli, María Isabel |
author_sort | Hernandez-Perez, Ines |
collection | PubMed |
description | Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion and migration, as well as failure to undergo epidermal to mesenchymal transition. However, the primary molecular role of kazrin, which might contribute to all these functions, has not been elucidated yet. We previously identified one of its isoforms, kazrin C, as a protein that potently inhibits clathrin-mediated endocytosis when overexpressed. We now generated kazrin knock-out mouse embryonic fibroblasts to investigate its endocytic function. We found that kazrin depletion delays juxtanuclear enrichment of internalized material, indicating a role in endocytic traffic from early to recycling endosomes. Consistently, we found that the C-terminal domain of kazrin C, predicted to be an intrinsically disordered region, directly interacts with several early endosome (EE) components, and that kazrin depletion impairs retrograde motility of these organelles. Further, we noticed that the N-terminus of kazrin C shares homology with dynein/dynactin adaptors and that it directly interacts with the dynactin complex and the dynein light intermediate chain 1. Altogether, the data indicate that one of the primary kazrin functions is to facilitate endocytic recycling by promoting dynein/dynactin-dependent transport of EEs or EE-derived transport intermediates to the recycling endosomes. |
format | Online Article Text |
id | pubmed-10181827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-101818272023-05-13 Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes Hernandez-Perez, Ines Rubio, Javier Baumann, Adrian Girao, Henrique Ferrando, Miriam Rebollo, Elena Aragay, Anna M Geli, María Isabel eLife Cell Biology Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion and migration, as well as failure to undergo epidermal to mesenchymal transition. However, the primary molecular role of kazrin, which might contribute to all these functions, has not been elucidated yet. We previously identified one of its isoforms, kazrin C, as a protein that potently inhibits clathrin-mediated endocytosis when overexpressed. We now generated kazrin knock-out mouse embryonic fibroblasts to investigate its endocytic function. We found that kazrin depletion delays juxtanuclear enrichment of internalized material, indicating a role in endocytic traffic from early to recycling endosomes. Consistently, we found that the C-terminal domain of kazrin C, predicted to be an intrinsically disordered region, directly interacts with several early endosome (EE) components, and that kazrin depletion impairs retrograde motility of these organelles. Further, we noticed that the N-terminus of kazrin C shares homology with dynein/dynactin adaptors and that it directly interacts with the dynactin complex and the dynein light intermediate chain 1. Altogether, the data indicate that one of the primary kazrin functions is to facilitate endocytic recycling by promoting dynein/dynactin-dependent transport of EEs or EE-derived transport intermediates to the recycling endosomes. eLife Sciences Publications, Ltd 2023-04-25 /pmc/articles/PMC10181827/ /pubmed/37096882 http://dx.doi.org/10.7554/eLife.83793 Text en © 2023, Hernandez-Perez et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Hernandez-Perez, Ines Rubio, Javier Baumann, Adrian Girao, Henrique Ferrando, Miriam Rebollo, Elena Aragay, Anna M Geli, María Isabel Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
title | Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
title_full | Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
title_fullStr | Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
title_full_unstemmed | Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
title_short | Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
title_sort | kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181827/ https://www.ncbi.nlm.nih.gov/pubmed/37096882 http://dx.doi.org/10.7554/eLife.83793 |
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