Introduction to the Special Issue of Cytoskeleton on the molecular and cell biology of septins

This Special Issue of Cytoskeleton was inspired by the 2021 EMBO Workshop entitled ‘Molecular and Cell Biology of Septins’ held in Berlin, Germany (https://meetings.embo.org/event/20-septins). As described in a meeting report (Baillet et al., 2021), the 2021 EMBO Workshop was transformative, enabling septin enthusiasts from around the globe to exchange ideas during a highly isolating period because of the COVID-19 pandemic. Septins, an evolutionarily conserved protein family essential for cell division, have been implicated in numerous cellular processes including cellular organisation, intracellular transport and morphogenesis. Although septins are a relatively poorly understood components of the cytoskeleton (as compared with actin or microtubules), the field of septin biology is blooming as much as ever. As our knowledge of septin structure and assembly improves, and more innovative technologies become available, new domains of study promise to illuminate septin roles in fundamental cellular processes and pathogenesis. This Special Issue of Cytoskeleton is a collection of 12 primary research articles and reviews serving to highlight the latest insights on the molecular and cell biology of septins. Septins were discovered by Leland Hartwell screening for cell division cycle (cdc) mutants in the budding yeast Saccharomyces cerevisiae. Septin genes have since been found in fungi and higher eukaryotes, yet their number ranges from 2 in Caenorhabditis elegans to 5 in Drosophila melanogaster to 13 in humans. Septins form heterooligomeric complexes, which assemble to form non-polar filaments and higher order structures including rings, collars and gauzes. In this Special Issue, Grupp et al. (2023) describe an in silico approach to determine septin subunit affinities based on their conserved guanine nucleotide-binding (G) domain, proposing a novel mechanism that helps to stabilise hetero-oligomeric complexes and filaments. de Freitas Fernandes et al. (2023) report the crystal structure of the heterodimer formed between G-domains of D. melanogaster septins Sep1 and Sep2. In sum, these two studies significantly enhance our understanding of molecular interactions involved in septin assembly and disassembly. The role of post-translational modifications (including ubiquitylation, SUMOylation, phosphorylation and acetylation) in septin biology has been of great interest for many years. In a review, Sharma and Menon (2023) discuss post-translational modifications of human septins and how this may impact their function. The BORG/Cdc42EP family, composed of five Rho GTPase binding proteins, is of historical interest to the field because of their fundamental interplay with the septin cytoskeleton. Here, Tomasso and Padrick (2023) review the role of BORG family proteins in cellular and disease physiology. Septins are widely recognised as components of the membrane cortex. Despite recent insights, the mechanisms underlying septin interactions with membranes are not fully understood. Benson and McMurray (2023) work with S. cerevisiae septins Cdc3 and Cdc10 to suggest what may restrict septin localisation to specific membranes. Perry et al. (2023) study C. elegans septins UNC-59 and UNC-61, implicate septins in the architecture of the germline syncytium (where many germs cells share a common cytoplasm), and propose different roles for the two different septins. Kim et al. (2023) discuss the role of septins and actin at endothelial cell–cell junctions and how they impact monolayer integrity. Taken together, we hope these three articles will inspire future studies concerning septin–membrane interactions in a wide variety of model systems. In the case of rice blast fungus Magnaporthae orzyae, septins are crucial for appressorium morphogenesis and plant invasion. Eisermann et al. (2023) review the role of septins in fungal pathogenesis and discuss septins as important targets for anti-fungal plant protection strategies. Septin–bacteria interactions have been the subject of intense investigation for more than 15 years. Using Shigella flexneri infection to stimulate septin-mediated immunity in human epithelial cells, Van Ngo et al. (2023) discover a new role for septins in caspase activity and apoptotic cell death. Next, Torraca et al. (2023) generate zebrafish (Danio rerio) null mutants of Sept6 and Sept15, showing that they are developmentally viable but more susceptible to S. flexneri infection than wild-type zebrafish. In the future, it will be important to study S. flexneri infection in vivo using these zebrafish models, and to discover new roles for septins in host defence from the single cell to whole animal level. Septins are enriched in the mammalian nervous system where they play key roles in neuronal development and function. Werner and Yadav (2023) provide an overview of kinases that interact with and phosphorylate mammalian septins, and how phosphoregulation may impact septin function in neuronal development and disease. In the peripheral nervous system, myelin is synthesised by Schwann cells. Using state-of-the-art mouse models, Martens et al. (2023) perform targeted inactivation of Sept2 and Sept9 in myelinating Schwann cells, discovering that SEPT2 (but not SEPT9) controls septin hetero-oligomeric complex formation and localisation in peripheral nervous system myelin in vivo. In conclusion, we thank all of our colleagues for their innovative and exciting contributions to this Special Issue of Cytoskeleton. We next look forward to the next gathering of our dynamic field. Received: 9 May 2023 Accepted: 10 May 2023