The septin family of proteins has fascinated cell biologists for decades due to the elaborate architecture they adopt in different eukaryotic cells. Whether they exist as rings, collars, or gauzes in different cell types and at different times in the cell cycle illustrates a complex series of regulation in structure. While the organization of different septin structures at the cortex of different cell types during the cell cycle has been described to various degrees, the exact structure and regulation at the filament level are still largely unknown. Recent advances in fluorescent and electron microscopy, as well as work in septin biochemistry, have allowed new insights into the aspects of septin architecture, remodeling, and function in many cell types. This mini-review highlights many of the recent findings with an emphasis on the budding yeast model.

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Septins form rod-shaped hetero-oligomeric 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 [1][2][3][4] to carry out a wide range of functions, including cytokinesis and cell morphogenesis. However, the architecture of septin higher-order assemblies and their control mechanisms, including regulation by conserved kinases [5,6], 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 [7][8][9]. The hourglass is remodeled into a double ring that sandwiches the actomyosin ring at the onset of cytokinesis [10][11][12][13]. How septins are assembled into a highly ordered hourglass structure at the division site [13] is largely unexplored. Here we show that the LKB1-like kinase Elm1, which has been implicated in septin organization [14], cell morphogenesis [15], and mitotic exit [16,17], specifically associates with the septin hourglass during the cell cycle and controls hourglass assembly and stability, especially for the daughter half, by regulating filament pairing and the functionality of its substrate, the septin-binding protein Bni5. This study illustrates how a protein kinase regulates septin architecture at the filament level and suggests that filament pairing is a highly regulated process during septin assembly and remodeling in vivo. ll

The septin family of proteins can assemble into filaments that further organize into different higher order structures to perform a variety of different functions in different cell types and organisms. In the budding yeast Saccharomyces cerevisiae, the septins localize to the presumptive bud site as a cortical ring prior to bud emergence, expand into an hourglass at the bud neck (cell division site) during bud growth, and finally “split” into a double ring sandwiching the cell division machinery during cytokinesis. While much work has been done to understand the functions and molecular makeups of these structures, the mechanisms underlying the transitions from one structure to another have largely remained elusive. Recent studies involving advanced imaging and in vitro reconstitution have begun to reveal the vast complexity involved in the regulation of these structural transitions, which defines the focus of discussion in this mini-review.

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.Mps1/TTK | centrosome | centriole | kinetochore | TPR