The LKB1-Like Kinase Elm1 Controls Septin Hourglass Assembly at the Cell Division Site by Promoting Filament Pairing

Abstract

Septins form rod-shaped heterooligomeric complexes that assemble into filaments and other higher-order structures such as rings or hourglasses at the cell division site in fungal and animal cells, at the annulus of spermatozoa or at the base of dendritic spines to carry out a wide range of functions including cytokinesis and cell morphogenesis. Mutations in human septins are associated with male infertility, many cancers, and neurodegenerative diseases. However, the architecture of the septin higher-order assemblies and their control mechanisms remain largely unknown. In the budding yeast Saccharomyces cerevisiae, the five mitotic septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1) localize to the bud neck and form an hourglass before cytokinesis that acts as a scaffold for proteins involved in multiple processes as well as a membrane diffusible barrier between the mother and developing bud. The hourglass is remodeled into a double ring that sandwiches the actomyosin ring at the onset of cytokinesis. How the septins are assembled into a highly ordered hourglass structure at the division site is largely unexplored. Here we show that the LKB1-like kinase Elm1, which has been implicated in septin organization, cell morphogenesis, and mitotic exit, specifically associates with the septin hourglass during the cell cycle, and controls hourglass assembly and stability, especially for the daughter half, by promoting filament pairing as well as recruitment of the septin-bundling protein Bni5 to the hourglass.