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.