GMF is a cofilin homolog that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation.
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.
Gandhi
Meghal
M
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA.
Smith
Benjamin A
BA
Bovellan
Miia
M
Paavilainen
Ville
V
Daugherty-Clarke
Karen
K
Gelles
Jeff
J
Lappalainen
Pekka
P
Goode
Bruce L
BL
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
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D051338:Cofilin 1; D020904:Glia Maturation Factor