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

Katarzyna Bogucka-Janczi1, Gregory Harms1,2, Marie-May Coissieux3

  • 1Cell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Elife
|April 14, 2023
PubMed

Insights

ERK3 acts as a guanine nucleotide exchange factor for CDC42 and phosphorylates ARP3, promoting filopodia and actin polymerization. This reveals a unique pathway controlling actin cytoskeleton dynamics.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The actin cytoskeleton is crucial for cellular functions and regulated by RhoGTPases and actin-binding proteins.
  • ERK3, an atypical MAPK, was previously shown to influence IL-8 production and chemotaxis.

Purpose of the Study:

  • To elucidate the role of ERK3 in regulating the actin cytoskeleton and cell motility.
  • To identify direct targets and mechanisms by which ERK3 controls actin dynamics.

Main Methods:

  • Guanine nucleotide exchange factor assays.
  • Western blotting and immunoprecipitation.
  • In vitro actin polymerization assays.
  • Cellular depletion studies (e.g., siRNA) and live-cell imaging.

Main Results:

  • ERK3 directly activates CDC42 and phosphorylates ARP3 subunit of the ARP2/3 complex.
  • ERK3 depletion impairs RAC1/CDC42 activation, F-actin content, filopodia formation, and cell migration.
  • ERK3 binds ARP2/3 complex and enhances actin polymerization in vitro.
  • ERK3 kinase activity is essential for actin-rich protrusion formation.

Conclusions:

  • ERK3 plays a novel, direct role in controlling actin cytoskeleton organization and cell migration.
  • ERK3 functions as a guanine nucleotide exchange factor and kinase to regulate actin dynamics.
  • This study uncovers a unique signaling pathway involving ERK3 in actin-dependent cellular processes.
Keywords:
Arp2/3ERK3MAPKRhoGTPasesactin polymerizationcancer biologycell biologycell shape /migrationhumanmouse

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