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

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.