Abstract
Septins are filamentous guanosine triphosphatase-binding proteins that are required for cytokinesis in a wide range of organisms from yeast to man. Several septins, including SEPT9, have been found to be altered in cancers, but their roles in malignancy and cytokinesis remain unclear. It is known that they assemble into rod-shaped oligomeric complexes that join end-on-end to form filaments, but whether SEPT9 incorporates into these complexes and how it does so are unanswered questions. We used tandem affinity purification of mammalian septin complexes to show that SEPT9 occupies a terminal position in an octameric septin complex. A mutant SEPT9, which cannot self-associate, disrupted septin filament formation and resulted in late abscission defects during cytokinesis but did not affect septin-dependent steps earlier in mitosis. These data suggest that mammalian SEPT9 holds a terminal position in the septin octamers, mediating abscission-specific polymerization during cytokinesis.