Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes

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

The following data sets were generated

Article and author information

Author details

  1. Ines Hernandez-Perez

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    Competing interests
    No competing interests declared.
  2. Javier Rubio

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0320-5100
  3. Adrian Baumann

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    Competing interests
    No competing interests declared.
  4. Henrique Girao

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    Competing interests
    No competing interests declared.
  5. Miriam Ferrando

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    Competing interests
    No competing interests declared.
  6. Elena Rebollo

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    Competing interests
    No competing interests declared.
  7. Anna M Aragay

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    For correspondence
    aarbmc@ibmb.csic.es
    Competing interests
    No competing interests declared.
  8. María Isabel Geli

    Instituto de Biología Molecular de Barcelona, Barcelona, Spain
    For correspondence
    mgfbmc@ibmb.csic.es
    Competing interests
    María Isabel Geli, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3452-6700

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

  1. Kassandra M Ori-McKenney, University of California, United States

Version history

  1. Preprint posted: August 31, 2021 (view preprint)
  2. Received: September 29, 2022
  3. Accepted: April 24, 2023
  4. Accepted Manuscript published: April 25, 2023 (version 1)
  5. 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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  1. Ines Hernandez-Perez
  2. Javier Rubio
  3. Adrian Baumann
  4. Henrique Girao
  5. Miriam Ferrando
  6. Elena Rebollo
  7. Anna M Aragay
  8. María Isabel Geli
(2023)
Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes
eLife 12:e83793.
https://doi.org/10.7554/eLife.83793

Share this article

https://doi.org/10.7554/eLife.83793

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