title: GMF is a cofilin homolog that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation.
abstract: Cell locomotion and endocytosis are powered by the rapid polymerization and turnover of branched actin filament networks nucleated by Arp2/3 complex. 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. Here, we investigated the function of a conserved homolog of ADF/cofilin, glia maturation factor (GMF). 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.
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA.
authors.forename: Meghal
authors.initials: M
authors.lastname: Gandhi
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Smith
authors.forename: Miia
authors.initials: M
authors.lastname: Bovellan
authors.forename: Ville
authors.initials: V
authors.lastname: Paavilainen
authors.forename: Karen
authors.initials: K
authors.lastname: Daugherty-Clarke
authors.forename: Jeff
authors.initials: J
authors.lastname: Gelles
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Goode
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D051338:Cofilin 1 / Q000235:genetics; D020904:Glia Maturation Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017385:Sequence Homology
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D051338:Cofilin 1; D020904:Glia Maturation Factor