The septins.
Ontology highlight
ABSTRACT:
SUBMITTER: Kinoshita M
PROVIDER: S-EPMC329110 | biostudies-literature | 2003
REPOSITORIES: biostudies-literature
Publications
The septins are guanine-nucleotide binding proteins that mostly form filaments. They are important in cytokinesis and also have roles in sporulation in yeasts and embryonic development and in the nervous system in animals. ...[more]
Similar Datasets
Project description:There are 10 known mammalian septin genes, some of which produce multiple splice variants. The current nomenclature for the genes and gene products is very confusing, with several different names having been given to the same gene product and distinct names given to splice variants of the same gene. Moreover, some names are based on those of yeast or Drosophila septins that are not the closest homologues. Therefore, we suggest that the mammalian septin field adopt a common nomenclature system, based on that adopted by the Mouse Genomic Nomenclature Committee and accepted by the Human Genome Organization Gene Nomenclature Committee. The human and mouse septin genes will be named SEPT1-SEPT10 and Sept1-Sept10, respectively. Splice variants will be designated by an underscore followed by a lowercase "v" and a number, e.g., SEPT4_v1.
| S-EPMC138619 | biostudies-literature
Project description:Septins, a unique cytoskeletal component associated with cellular membranes, are increasingly recognized as having important roles in host defense against bacterial infection. A role for septins during invasion of Listeria monocytogenes into host cells was first proposed in 2002. Since then, work has shown that septins assemble in response to a wide variety of invasive bacterial pathogens, and septin assemblies can have different roles during the bacterial infection process. Here we review the interplay between septins and bacterial pathogens, highlighting septins as a structural determinant of host defense. We also discuss how investigation of septin assembly in response to bacterial infection can yield insight into basic cellular processes including phagocytosis, autophagy, and mitochondrial dynamics.
| S-EPMC5104955 | biostudies-literature
Project description:We describe phylogenetic and functional studies of three septins in the free-living ciliate Tetrahymena thermophila. Both deletion and overproduction of septins led to vacuolization of mitochondria, destabilization of the nuclear envelope, and increased autophagy. All three green fluorescent protein-tagged septins localized to mitochondria. Specific septins localized to the outer mitochondrial membrane, to septa formed during mitochondrial scission, or to the mitochondrion-associated endoplasmic reticulum. The only other septins known to localize to mitochondria are human ARTS and murine M-septin, both alternatively spliced forms of Sep4 (S. Larisch, Cell Cycle 3:1021-1023, 2004; S. Takahashi, R. Inatome, H. Yamamura, and S. Yanagi, Genes Cells 8:81-93, 2003). It therefore appears that septins have been recruited to mitochondrial functions independently in at least two eukaryotic lineages and in both cases are involved in apoptotic events.
| S-EPMC2519767 | biostudies-literature
Project description:BackgroundSeptins are conserved GTPases that form filaments and are required in many organisms for several processes including cytokinesis. We previously identified SEPT9 associated with phagosomes containing latex beads coated with the Listeria surface protein InlB.Methodology/principal findingsHere, we investigated septin function during entry of invasive bacteria in non-phagocytic mammalian cells. We found that SEPT9, and its interacting partners SEPT2 and SEPT11, are recruited as collars next to actin at the site of entry of Listeria and Shigella. SEPT2-depletion by siRNA decreased bacterial invasion, suggesting that septins have roles during particle entry. Incubating cells with InlB-coated beads confirmed an essential role for SEPT2. Moreover, SEPT2-depletion impaired InlB-mediated stimulation of Met-dependent signaling as shown by FRET.Conclusions/significanceTogether these findings highlight novel roles for SEPT2, and distinguish the roles of septin and actin in bacterial entry.
| S-EPMC2626286 | biostudies-literature
Project description:Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions extending above or below neighboring cells. Vascular endothelial cadherin (VE-cadherin) was present at cell junctions, with a membrane-associated layer of F-actin. Septins localized at cell-junction membranes, in patterns distinct from VE-cadherin and F-actin. Septins assumed curved and scallop-shaped patterns at junctions, especially in regions of positive membrane curvature associated with actin-rich membrane protrusions. Depletion of septins led to disrupted morphology of VE-cadherin junctions and increased expression of VE-cadherin. In videos, septin-depleted cells displayed remodeling at cell junctions; regions with VE-cadherin were broader, and areas with membrane ruffling were wider. Septin depletion and junction disruption led to functional loss of junctional integrity, revealed by decreased transendothelial electric resistance and increased transmigration of immune cells. We conclude that septins, as cytoskeletal elements associated with the plasma membrane, are important for cell junctions and junctional integrity of endothelial monolayers, functioning at regions of positive curvature in support of actin-rich protrusions to promote cadherin-based cell junctions.
| S-EPMC6080707 | biostudies-literature
Project description:Septins form a subfamily of highly related GTP-binding proteins conserved from eukaryotic protists to mammals. In most cases, septins function in close association with cell membranes and the actin and microtubule cytoskeleton to regulate a wide variety of key cellular processes. Further underscoring their importance, septin abnormalities are associated with several human diseases. Remarkably, septins have the ability to polymerize into assemblies of different sizes in vitro and in vivo. In cells, these structures act in the formation of diffusion barriers and scaffolds that maintain subcellular polarity. Here, we focus on the emerging roles of vertebrate septins in ciliogenesis, neurogenesis, tumorigenesis and host-pathogen interactions, and discuss whether unifying themes underlie the molecular function of septins in health and disease.
| S-EPMC3207108 | biostudies-literature
Project description:The septins are a family of homologous proteins that were originally identified in Saccharomyces cerevisiae, where they are associated with the "neck filaments" and are involved in cytokinesis and other aspects of the organization of the cell surface. We report here the identification of Sep1, a Drosophila melanogaster septin, based on its homology to the yeast septins. The predicted Sep1 amino acid sequence is 35-42% identical to the known S. cerevisiae septins; 52% identical to Pnut, a second D. melanogaster septin; and 53-73% identical to the known mammalian septins. Sep1-specific antibodies have been used to characterize its expression and localization. The protein is concentrated at the leading edge of the cleavage furrows of dividing cells and cellularizing embryos, suggesting a role in furrow formation. Other aspects of Sep1 localization suggest roles not directly related to cytokinesis. For example, Sep1 exhibits orderly, cell-cycle-coordinated rearrangements within the cortex of syncytial blastoderm embryos and in the cells of post-gastrulation embryos; Sep1 is also concentrated at the leading edge of the epithelium during dorsal closure in the embryo, in the neurons of the embryonic nervous system, and at the baso-lateral surfaces of ovarian follicle cells. The distribution of Sep1 typically overlaps, but is distinct from, that of actin. Both immunolocalization and biochemical experiments show that Sep1 is intimately associated with Pnut, suggesting that the Drosophila septins, like those in yeast, function as part of a complex.
| S-EPMC301337 | biostudies-other
Project description:Septins are a family of membrane-associated cytoskeletal GTPases that play crucial roles in various cellular processes, such as cell division, phagocytosis, and organelle fission. Despite their importance, the evolutionary origins and ancestral function of septins remain unclear. In opisthokonts, septins form five distinct groups of orthologs, with subunits from multiple groups assembling into heteropolymers, thus supporting their diverse molecular functions. Recent studies have revealed that septins are also conserved in algae and protists, indicating an ancient origin from the last eukaryotic common ancestor. However, the phylogenetic relationships among septins across eukaryotes remained unclear. Here, we expanded the list of non-opisthokont septins, including previously unrecognized septins from rhodophyte red algae and glaucophyte algae. Constructing a rooted phylogenetic tree of 254 total septins, we observed a bifurcation between the major non-opisthokont and opisthokont septin clades. Within the non-opisthokont septins, we identified three major subclades: Group 6 representing chlorophyte green algae (6A mostly for species with single septins, 6B for species with multiple septins), Group 7 representing algae in chlorophytes, heterokonts, haptophytes, chrysophytes, and rhodophytes, and Group 8 representing ciliates. Glaucophyte and some ciliate septins formed orphan lineages in-between all other septins and the outgroup. Combining ancestral-sequence reconstruction and AlphaFold predictions, we tracked the structural evolution of septins across eukaryotes. In the GTPase domain, we identified a conserved GAP-like arginine finger within the G-interface of at least one septin in most algal and ciliate species. This residue is required for homodimerization of the single Chlamydomonas septin, and its loss coincided with septin duplication events in various lineages. The loss of the arginine finger is often accompanied by the emergence of the α0 helix, a known NC-interface interaction motif, potentially signifying the diversification of septin-septin interaction mechanisms from homo-dimerization to hetero-oligomerization. Lastly, we found amphipathic helices in all septin groups, suggesting that curvature-sensing is an ancestral trait of septin proteins. Coiled-coil domains were also broadly distributed, while transmembrane domains were found in some septins in Group 6A and 7. In summary, this study advances our understanding of septin distribution and phylogenetic groupings, shedding light on their ancestral features, potential function, and early evolution.
| S-EPMC10996617 | biostudies-literature
Project description:Apoptosis is a form of regulated cell death essential for tissue homeostasis and embryonic development. Apoptosis also plays a key role during bacterial infection, yet some intracellular bacterial pathogens (such as Shigella flexneri, whose lipopolysaccharide can block apoptosis) can manipulate cell death programs as an important survival strategy. Septins are a component of the cytoskeleton essential for mitochondrial dynamics and host defense, however, the role of septins in regulated cell death is mostly unknown. Here, we discover that septins promote mitochondrial (i.e., intrinsic) apoptosis in response to treatment with staurosporine (a pan-kinase inhibitor) or etoposide (a DNA topoisomerase inhibitor). Consistent with a role for septins in mitochondrial dynamics, septins promote the release of mitochondrial protein cytochrome c in apoptotic cells and are required for the proteolytic activation of caspase-3, caspase-7, and caspase-9 (core components of the apoptotic machinery). Apoptosis of HeLa cells induced in response to infection by S. flexneri ΔgalU (a lipopolysaccharide mutant unable to block apoptosis) is also septin-dependent. In vivo, zebrafish larvae are significantly more susceptible to infection with S. flexneri ΔgalU (as compared to infection with wildtype S. flexneri), yet septin deficient larvae are equally susceptible to infection with S. flexneri ΔgalU and wildtype S. flexneri. These data provide a new molecular framework to understand the complexity of mitochondrial apoptosis and its ability to combat bacterial infection.
| S-EPMC10952901 | biostudies-literature
Project description:Septins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that the SEPT9 gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclasts in vitro suggesting a role for septins in bone resorption. Attesting to this, conditional deletion of Sept9 in mice leads to elevated levels of trabecular bone and diminished femoral growth in vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone resorption.
| S-EPMC6115361 | biostudies-other