Septine

Septins are cytoskeletal proteins that form the fourth major component of the cytoskeleton alongside microtubules and intermediate filaments. They self-assemble into hetero-oligomeric structures including filaments and ring or cage-like structures that scaffold cytoskeletal proteins during cell division and compartmentalize the cell membrane.

Septin monomers contain three distinct regions: a variable N-terminal head with a lipid-binding polybasic region that interacts with phosphoinositides, a conserved central GTP-binding domain with three GTP-binding motifs, and a coiled-coil C-terminal tail that enables inter-filament bridges and filament assembly.

GTP binding to the central GTP-binding domain and its rapid hydrolysis facilitate septin dimer formation. GDP-bound septin dimers then polymerize into linear septin filaments. The septin unique region within the GTP-binding domain helps drive septin filament formation and stabilize these polymeric structures.

The N-terminal polybasic region of septins binds to phosphoinositides in the cell membrane, promoting polymerization of septin filaments. This interaction enables membrane compartmentalization and allows septins to form ring-like structures at specific cellular locations, such as the budding neck during yeast cell division.

Septins are classified into four groups based on protein sequence similarity: SEPT2, SEPT3, SEPT6, and SEPT7. The number of septins varies by organism; Saccharomyces cerevisiae has seven septins, while humans have thirteen distributed across these four groups with distinct sequence characteristics.

Septin filaments assemble through the coiled-coil C-terminal tail region, which forms inter-filament bridges connecting different septin filaments. The lipid-binding N-terminal region anchors filaments to the cell membrane, while the GTP-binding domain regulates polymerization dynamics through nucleotide hydrolysis and dimer formation.

In 1971, researchers studying Saccharomyces cerevisiae identified septin-related genes crucial for yeast cytokinesis. Fluorescence microscopy revealed these proteins localize as rings at the budding neck. John Pringle named them septins, and systematic characterization of these highly conserved cytoskeletal proteins began in the 1980s.