Fifteen formins for an actin filament: a molecular view on the regulation of human formins

Abstract

The regulation of the actin cytoskeleton is a key process for the stability and motility of eukaryotic cells. Besides the Arp2/3 complex and its nucleation promoting factors, WH2 domain-containing proteins and a diverse family of formin proteins have recently been recognized as actin nucleators and potent polymerization factors of actin filaments. Formins are defined by the presence of a catalytic formin homology 2 (FH2) domain, yet, the modular domain architecture appears significantly different for the eight formin families identified in humans. A diverse picture of protein localization, interaction partners and cell specific regulation emerged, suggesting various functions of formins in the building and maintenance of actin filaments. This review focuses on the domain architecture of human formins, the regulation mechanisms of their activation and the diversity in formin cellular functions.