MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-containing Arp2/3 complexes

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• The regulation of branched actin networks, crucial for cell motility and structure, is incompletely understood.
• The specific roles of actin-related protein 2/3 (Arp2/3) complex isoforms, such as Arp3 and Arp3B, in modulating actin network properties remain largely unexplored.

Purpose of the Study:

• To investigate the distinct contributions of Arp3 and Arp3B isoforms to actin assembly and disassembly dynamics.
• To elucidate the molecular mechanisms underlying differential Arp2/3 complex stability and actin network turnover.

Main Methods:

• Comparative analysis of actin assembly and disassembly kinetics using Arp3 and Arp3B isocomplexes.
• Investigating the role of methionine monooxygenase MICAL2, coronin 1C, and cortactin in regulating Arp2/3 complex function.
• Site-directed mutagenesis to probe the functional significance of specific methionine and threonine residues.

Main Results:

• Arp3 and Arp3B isocomplexes exhibit equal actin assembly efficiency but differ in branched network disassembly rates.
• Arp3B dissociates faster from actin networks than Arp3, and its depletion enhances actin stability.
• MICAL2-mediated oxidation of Arp3B at Met293, facilitated by coronin 1C and cortactin, promotes network disassembly.

Conclusions:

• Coronin 1C, cortactin, and MICAL2 form a complex to regulate branched actin network disassembly.
• Oxidation of Arp3B by MICAL2 is a key mechanism controlling actin network stability, distinct from Arp3's function.
• Understanding Arp2/3 complex isoform-specific regulation provides insights into dynamic actin cytoskeleton control.