The septin family of GTPases: architecture and dynamics

Key Points Septins comprise a conserved family of GTP-binding proteins that have multiple roles during cell division, cytoskeletal organization and membrane remodelling events. Individual septins form smaller core complexes both in vivo and in vitro and contain, depending on the organism, two, three or four septins, each present in two copies. Core complexes oligomerize to form higher-order structures in vivo . Electron microscopy and crystallographic studies have revealed that the septin core structure is mediated by interactions between GTP-binding domains across two distinct dimerization interfaces. Metazoan core complexes, in which the core complex architecture has been determined, oligomerize to form filaments across G-dimer interfaces, whereas the Saccharomyces cerevisiae complex forms complexes across the NC-dimer interface. The G-dimer interface of septin oligomers is similar to the dimerization interface that is observed for the related Toc GTPases, which suggests that mechanistic similarities may exist between these evolutionarily related GTPases. However, the functional consequences of GTP binding and hydrolysis by septins for complex formation remain mysterious. Septin core complexes form higher-order filaments that can dynamically engage the plasma membrane at the bud neck in S. cerevisiae , undergoing complex topological transitions during the cell cycle. It remains unclear how septin-filament assembly is regulated and precisely how GTP binding and hydrolysis, as well as protein cofactors, regulate the assembly and disassembly of septin structure in vivo . How do septins, GTP-binding proteins, function in a wide range of cellular processes, such as cell division, cytoskeletal organization and membrane remodelling? Electron microscopy and crystallographic studies provide a glimpse into septin-complex assembly that could answer this question. Septins comprise a conserved family of proteins that are found primarily in fungi and animals. These GTP-binding proteins have several roles during cell division, cytoskeletal organization and membrane-remodelling events. One factor that is crucial for their functions is the ordered assembly of individual septins into oligomeric core complexes that, in turn, form higher-order structures such as filaments, rings and gauzes. The molecular details of these interactions and the mechanism by which septin-complex assembly is regulated have remained elusive. Recently, the first detailed structural views of the se