Actin‐depolymerizing factor homology domain: A conserved fold performing diverse roles in cytoskeletal dynamics

Abstract

Actin filaments form contractile and protrusive structures that play central roles in many processes such as cell migration, morphogenesis, endocytosis, and cytokinesis. During these processes, the dynamics of the actin filaments are precisely regulated by a large array of actin‐binding proteins. The actin‐depolymerizing factor homology (ADF‐H) domain is a structurally conserved protein motif, which promotes cytoskeletal dynamics by interacting with monomeric and/or filamentous actin, and with the Arp2/3 complex. Despite their structural homology, the five classes of ADF‐H domain proteins display distinct biochemical activities and cellular roles, only parts of which are currently understood. ADF/cofilin promotes disassembly of aged actin filaments, whereas twinfilin inhibits actin filament assembly via sequestering actin monomers and interacting with filament barbed ends. GMF does not interact with actin, but instead binds Arp2/3 complex and promotes dissociation of Arp2/3‐mediated filament branches. Abp1 and drebrin are multidomain proteins that interact with actin filaments and regulate the activities of other proteins during various actin‐dependent processes. The exact function of coactosin is currently incompletely understood. In this review article, we discuss the biochemical functions, cellular roles, and regulation of the five groups of ADF‐H domain proteins. © 2011 Wiley‐Liss, Inc.

Glia Maturation Factor (GMF) Interacts with Arp2/3 Complex in a Nucleotide State-dependent Manner

“…Thus, human GMF␤ and GMF␥, which share 17.6 and 15.5% sequence identities with human cofilin-1, respectively, display a three-dimensional fold similar to that of other members of the ADF/cofilin family (6). Members of this family, including twinfilin, Abp1, drebrin, and coactosin, are generally implicated in regulation of actin cytoskeleton dynamics (1).…”

“…2 is a 17-kDa protein conserved from yeast to human (1). Mammals express two GMF isoforms, GMF␤ and GMF␥, which share 82% sequence identity but display different tissue distributions (2).…”

“…GMF␥ is expressed in microvascular endothelial and inflammatory cells and has been implicated in promoting neutrophil and T cell migration (4,5). GMF is a member of the actin-depolymerizing factor (ADF)/cofilin family (1). Thus, human GMF␤ and GMF␥, which share 17.6 and 15.5% sequence identities with human cofilin-1, respectively, display a three-dimensional fold similar to that of other members of the ADF/cofilin family (6).…”

Glucagon-Like Peptide-1 Protects Human Islets against Cytokine-Mediated β-Cell Dysfunction and Death: A Proteomic Study of the Pathways Involved

“…17 The dynamic assembly and disassembly of filaments and the formation of larger scale filament structures, F-actin out of monomeric G-actin, are crucial aspects of the function of actin and are therefore under scrupulous control by over 100 actinbinding proteins. 47 In this study, we identified multiple cytokine-and GLP-1-responsive proteins such as actin-related protein 3 (ARP3), F-actin-capping protein subunit beta (CAPZB), and heat shock protein beta-1 (HSPB1), which are involved in F-actin polymerization 48,49 as well as proteins such as tropomodulin-3 (TMOD3), which is involved in actin depolymerization. 50 Cytokine-mediated down-regulation of these proteins in human β-cells most likely disrupts the dynamic equilibrium between monomeric G-actin and filamentous F-actin and in this way inhibits GSIS.…”

The role of the drebrin/EB3/Cdk5 pathway in dendritic spine plasticity, implications for Alzheimer’s disease

“…1, Larbolette et al, 1999;Kessels et al, 2000;Xu and Stamnes, 2006). The ADFH domain is structurally conserved among five families of actin-binding proteins including actin depolymerising factor (ADF)/cofilin, Abp1 and twinfillin (Poukkula et al, 2011). In these other families, the ADFH domain binds globular (G)-or F-actin but there is no evidence of actin binding by the drebrin ADFH domain Chew et al, 2005;Xu and Stamnes, 2006;Grintsevich et al, 2010;Worth et al, 2013).…”