ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization

  1. Katarzyna Bogucka-Janczi
  2. Gregory Harms
  3. Mary May-Coissieux
  4. Mohamed Bentires-Alj
  5. Bernd Thiede
  6. Krishnaraj Rajalingam  Is a corresponding author
  1. Johannes Gutenberg University of Mainz, Germany
  2. University Hospital of Basel, Switzerland
  3. University of Basel, Switzerland
  4. University of Oslo, Norway

Abstract

The actin cytoskeleton is tightly controlled by RhoGTPases, actin binding-proteins and nucleation-promoting factors to perform fundamental cellular functions. We have previously shown that ERK3, an atypical MAPK controls IL-8 production and chemotaxis52. Here, we show in human cells that, ERK3 directly acts as a guanine nucleotide exchange factor for CDC42and phosphorylates the ARP3 subunit of the ARP2/3 complex at S418 to promote filopodia formation and actin polymerization, respectively. Consistently, depletion of ERK3 prevented both basal and EGF-dependent RAC1 and CDC42 activation, maintenance of F-actin content, filopodia formation and epithelial cell migration. Further, ERK3 protein bound directly to the purified ARP2/3 complex and augmented polymerization of actin in vitro. ERK3 kinase activity was required for the formation of actin-rich protrusions in mammalian cells. These findings unveil a fundamentally unique pathway employed by cells to control actin-dependent cellular functions.

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Article and author information

Author details

  1. Katarzyna Bogucka-Janczi

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6254-3359
  2. Gregory Harms

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    No competing interests declared.
  3. Mary May-Coissieux

    Department of Biomedicine, University Hospital of Basel, Basel, Switzerland
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5017-5253
  4. Mohamed Bentires-Alj

    Department of Biomedicine, University of Basel, Basel, Switzerland
    Competing interests
    No competing interests declared.
  5. Bernd Thiede

    Department of Bioscience, University of Oslo, Oslo, Norway
    Competing interests
    No competing interests declared.
  6. Krishnaraj Rajalingam

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    For correspondence
    krishna@uni-mainz.de
    Competing interests
    Krishnaraj Rajalingam, KR is the founder and MD of KHR Biotec GmbH.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4175-9633

Funding

Else Kröner-Fresenius-Stiftung (SUN-MAPK)

  • Katarzyna Bogucka-Janczi
  • Gregory Harms

Deutsche Forschungsgemeinschaft (CRC1292)

  • Katarzyna Bogucka-Janczi
  • Krishnaraj Rajalingam

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The animal experiments were performed as per the guideliens of University MEdical center Basel

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Preprint posted: October 13, 2022 (view preprint)
  2. Received: November 29, 2022
  3. Accepted: April 13, 2023
  4. Accepted Manuscript published: April 14, 2023 (version 1)
  5. Accepted Manuscript updated: April 17, 2023 (version 2)
  6. Version of Record published: May 17, 2023 (version 3)

Copyright

© 2023, Bogucka-Janczi 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. Katarzyna Bogucka-Janczi
  2. Gregory Harms
  3. Mary May-Coissieux
  4. Mohamed Bentires-Alj
  5. Bernd Thiede
  6. Krishnaraj Rajalingam
(2023)
ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization
eLife 12:e85167.
https://doi.org/10.7554/eLife.85167

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