Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes
- Instituto de Biología Molecular de Barcelona, Spain
Abstract
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.
Data availability
All data presented or analyzed in the manuscript has been loaded in Dryad DOI https://doi.org/10.5061/dryad.k6djh9w9q
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Data from: Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomesDryad Digital Repository, doi:10.5061/dryad.k6djh9w9q.
Article and author information
Author details
Funding
Agencia Estatal de Investigación (BFU2017-82959-P)
- María Isabel Geli
Agencia Estatal de Investigación (PID2020-120053GB-I00)
- María Isabel Geli
Ministerio de Ciencia, Innovación y Universidades (EQC2018-004541 EU FeDer)
- Elena Rebollo
Consejo Superior de Investigaciones Científicas (CSIC1501/18)
- Elena Rebollo
Ministerio de Ciencia, Innovación y Universidades (BES-2015-071691)
- Ines Hernandez-Perez
Ministerio de Ciencia, Innovación y Universidades (BES-2015-071691)
- Adrian Baumann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kassandra M Ori-McKenney, University of California, United States
Version history
- Preprint posted: August 31, 2021 (view preprint)
- Received: September 29, 2022
- Accepted: April 24, 2023
- Accepted Manuscript published: April 25, 2023 (version 1)
- Version of Record published: May 12, 2023 (version 2)
Copyright
© 2023, Hernandez-Perez et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes
eLife 12:e83793.
https://doi.org/10.7554/eLife.83793
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