Abstract
Cell locomotion and endocytosis are powered by the rapid polymerization and turnover of branched actin filament networks nucleated by Arp2/3 complex [
1]. Although a large number of cellular factors have been identified that stimulate Arp2/3 complex-mediated actin nucleation, only a small number of studies so far have addressed which factors promote actin network debranching [
2–4]. Here, we investigated the function of a conserved homolog of ADF/cofilin, glia maturation factor (GMF) [
5, 6]. We found that
S. cerevisiae GMF (also called Aim7) localizes in vivo to cortical actin patches and displays synthetic genetic interactions with ADF/cofilin. However, GMF lacks detectable actin binding or severing activity and instead binds tightly to Arp2/3 complex. Using in vitro evanescent wave microscopy, we demonstrated that GMF potently stimulates debranching of actin filaments produced by Arp2/3 complex. Further, GMF inhibits nucleation of new daughter filaments. Together, these data suggest that GMF binds Arp2/3 complex to both “prune” daughter filaments at the branch points and inhibit new actin assembly. These activities and its genetic interaction with ADF/cofilin support a role for GMF in promoting the remodeling and/or disassembly of branched networks. Therefore, ADF/cofilin and GMF, members of the same superfamily, appear to have evolved to interact with actin and actin-related proteins, respectively, and to make mechanistically distinct contributions to the remodeling of cortical actin structures.
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► Yeast GMF localizes to actin patches and genetically interacts with ADF/cofilin ► GMF binds to Arp2/3 complex but not actin ► GMF inhibits actin nucleation and stimulates filament debranching ► GMF and cofilin use distinct mechanisms to remodel dendritic actin networks