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Two ligands of Arp2/3 complex, yeast coronin and GMF, interact and synergize in pruning branched actin networks
Journal article   Open access   Peer reviewed

Two ligands of Arp2/3 complex, yeast coronin and GMF, interact and synergize in pruning branched actin networks

Neha Koundinya, Rey M Aguilar, Kathryn Wetzel, Meagan R Tomasso, Priyashree Nagarajan, Emma R McGuirk, Shae B Padrick and Bruce L Goode
The Journal of biological chemistry, v 301(3), 108191
16 Jan 2025
PMID: 39826693
url
https://doi.org/10.1016/j.jbc.2025.108191View
Published, Version of Record (VoR) Open

Abstract

Arp2/3 complex GMF actin yeast coronin
The rapid turnover of branched actin networks underlies key in vivo processes such as lamellipodial extension, endocytosis, phagocytosis, and intracellular transport. However, our understanding of the mechanisms used to dissociate, or 'prune', branched filaments has remained limited. Glia maturation factor (GMF) is a cofilin family protein that binds to Arp2/3 complex and catalyzes branch dissociation. Here, we show that another ligand of Arp2/3 complex, S. cerevisiae coronin (Crn1), enhances Gmf1-mediated debranching by 8-10 fold, and that these effects depend on Arp2/3-binding 'C' and 'A' motifs in Crn1. Further, we show that Crn1 directly binds with high affinity (K = 1.4 nM) to S. cerevisiae GMF (Gmf1), and together they form a stable ternary Crn1-Gmf1-Arp2/3 complex in solution. Using single molecule analysis, we show that Gmf1 binds transiently and multiple times to F-actin branch junctions prior to debranching. These and other results suggest a mechanism of mutual recruitment, in which Crn1 increases the on-rate of Gmf1 for branch junctions and Gmf1 blocks Crn1 binding to actin filament sides, increasing its availability to bind branch junctions. Taken together, these observations reveal an unanticipated mechanism in which two distinct ligands of Arp2/3 complex bind to each other and synergize to prune actin branches.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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