# Septin > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Septin > Markdown URL: https://mediated.wiki/source/Septin.md > Source: https://en.wikipedia.org/wiki/Septin > Source revision: 1336167190 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{short description|Family of proteins}} {{Pfam box |Symbol = Cell_Div_GTP_bd |Name = Cell division/GTP binding protein |Pfam = PF00735 |Pfam_clan = CL0023 |InterPro = IPR000038 |PROSITE = |PDB = }} '''Septins''' are a group of [GTP](/source/guanosine_triphosphate)-[binding protein](/source/molecular_binding)s [expressed](/source/gene_expression) in all [eukaryotic cells](/source/eukaryote) except [plant](/source/plant)s.{{cite journal | vauthors = Weirich CS, Erzberger JP, Barral Y | title = The septin family of GTPases: architecture and dynamics | journal = Nat. Rev. Mol. Cell Biol. | volume = 9 | issue = 6 | pages = 478–89 | year = 2008 | pmid = 18478031 | doi = 10.1038/nrm2407 | s2cid = 2640351 }}{{cite journal | vauthors = Douglas LM, Alvarez FJ, McCreary C, Konopka JB | title = Septin function in yeast model systems and pathogenic fungi | journal = Eukaryotic Cell | volume = 4 | issue = 9 | pages = 1503–12 | year = 2005 | pmid = 16151244 | pmc = 1214204 | doi = 10.1128/EC.4.9.1503-1512.2005 }} Different septins form [protein complex](/source/protein_complex)es with each other. These complexes can further assemble into filaments, rings and gauzes. Assembled as such, septins function in cells by localizing other [proteins](/source/proteins), either by providing a scaffold to which proteins can attach, or by forming a barrier preventing the [diffusion](/source/diffusion) of molecules from one compartment of the cell to another,{{cite journal | vauthors = Mostowy S, Cossart P | title = Septins: the fourth component of the cytoskeleton | journal = Nat. Rev. Mol. Cell Biol. | volume = 13 | issue = 3 | pages = 183–94 | year = 2012 | pmid = 22314400 | doi = 10.1038/nrm3284 | s2cid = 2418522 }}{{cite journal | vauthors = Kinoshita M | title = Diversity of septin scaffolds | journal = Curr. Opin. Cell Biol. | volume = 18 | issue = 1 | pages = 54–60 | year = 2006 | pmid = 16356703 | doi = 10.1016/j.ceb.2005.12.005 }} or in the [cell cortex](/source/cell_cortex) as a barrier to the diffusion of membrane-bound proteins. Septins have been implicated in the localization of cellular processes at the site of [cell division](/source/cell_division), and at the [cell membrane](/source/cell_membrane) at sites where specialized structures like [cilia](/source/cilium) or [flagella](/source/flagella) are attached to the cell body. In yeast cells, they compartmentalize parts of the cell and build scaffolding to provide structural support during cell division at the [septum](/source/septum_(cell_biology)), from which they derive their name. Research in human cells suggests that septins build cages around [pathogenic bacteria](/source/pathogenic_bacteria), that immobilize and prevent them from invading other cells.{{cite journal | vauthors = Mascarelli A | title = Septin proteins take bacterial prisoners: A cellular defence against microbial pathogens holds therapeutic potential | journal = Nature | date = December 2011 | doi = 10.1038/nature.2011.9540 | s2cid = 85080734 | doi-access = free }} As filament forming proteins, septins can be considered part of the [cytoskeleton](/source/cytoskeleton). Apart from forming non-polar filaments, septins associate with [cell membrane](/source/cell_membrane)s, the cell cortex, [actin filament](/source/actin_filament)s and [microtubule](/source/microtubule)s.{{cite journal |last1=Bridges |first1=AA |last2=Gladfelter |first2=AS |title=Septin Form and Function at the Cell Cortex. |journal=The Journal of Biological Chemistry |date=10 July 2015 |volume=290 |issue=28 |pages=17173–80 |doi=10.1074/jbc.R114.634444 |pmid=25957401|pmc=4498057 |doi-access=free }} ==Structure== thumb|schematic domain structure of septin polypeptide chain thumb|a) schematic of septin molecule with GTP binding domain to one side and the N and C termini of the polypeptide chain to the other
b) schematic of septin heterohexameric complex (of human septins), where different septins bind to each other via their GTP binding domains or via the N and C termini. Note the symmetry of the complex
c) schematic how septin complexes could align to form septin filaments Septins are [P-Loop](/source/Walker_motifs)-NTPase [protein](/source/protein)s that range in weight from 30-65 kDa. Septins are highly conserved between different eukaryotic species. They are composed of a variable-length proline rich [N-terminus](/source/N-terminus) with a [basic](/source/Base_(chemistry)) [phosphoinositide](/source/phosphoinositide) [binding](/source/Binding_(molecular)) [motif](/source/sequence_motif) important for membrane association, a [GTP-binding domain](/source/G_protein), a highly conserved Septin Unique Element domain, and a [C-terminal](/source/C-terminal) extension including a [coiled coil](/source/coiled_coil) domain of varying length. Septins interact either via their respective GTP-binding domains, or via both their N- and C-termini. Different organisms express a different number of septins, and from those symmetric oligomers are formed. For example, in yeast the octameric complex formed is Cdc11-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11.{{Cite journal|last1=Bertin|first1=A.|last2=McMurray|first2=M. A.|last3=Grob|first3=P.|last4=Park|first4=S.-S.|last5=Garcia|first5=G.|last6=Patanwala|first6=I.|last7=Ng|first7=H.-l.|last8=Alber|first8=T.|last9=Thorner|first9=J.|last10=Nogales|first10=E.|date=2008-06-12|title=Saccharomyces cerevisiae septins: Supramolecular organization of heterooligomers and the mechanism of filament assembly|journal=Proceedings of the National Academy of Sciences|volume=105|issue=24|pages=8274–8279|doi=10.1073/pnas.0803330105|pmid=18550837|pmc=2426963|bibcode=2008PNAS..105.8274B|issn=0027-8424|doi-access=free}} In humans, hexameric or octameric complexes are possible. Initially, it was indicated that the human complex was Sept7-Sept6-Sept2-Sept2-Sept6-Sept7;{{Cite journal|last1=Sirajuddin|first1=Minhajuddin|last2=Farkasovsky|first2=Marian|last3=Hauer|first3=Florian|last4=Kühlmann|first4=Dorothee|last5=Macara|first5=Ian G.|last6=Weyand|first6=Michael|last7=Stark|first7=Holger|last8=Wittinghofer|first8=Alfred|date=2007-07-18|title=Structural insight into filament formation by mammalian septins|journal=Nature|volume=449|issue=7160|pages=311–315|doi=10.1038/nature06052|pmid=17637674|bibcode=2007Natur.449..311S|issn=0028-0836}} but recently this order has been revised to Sept2-Sept6-Sept7-Sept7-Sept6-Sept2{{Cite journal|last1=Mendonça|first1=Deborah C.|last2=Macedo|first2=Joci N.|last3=Guimarães|first3=Samuel L.|last4=Barroso da Silva|first4=Fernando L.|last5=Cassago|first5=Alexandre|last6=Garratt|first6=Richard C.|last7=Portugal|first7=Rodrigo V.|last8=Araujo|first8=Ana P. U.|date=September 2019|title=A revised order of subunits in mammalian septin complexes|journal=Cytoskeleton|volume=76|issue=9–10|pages=457–466|doi=10.1002/cm.21569|pmid=31608568|s2cid=204536675|issn=1949-3584}} (or Sept2-Sept6-Sept7-Sept3-Sept3-Sept7-Sept6-Sept2{{Cite journal|last1=Soroor|first1=Forooz|last2=Kim|first2=Moshe S.|last3=Palander|first3=Oliva|last4=Balachandran|first4=Yadu|last5=Collins|first5=Richard|last6=Benlekbir|first6=Samir|last7=Rubinstein|first7=John|last8=Trimble|first8=William S.|title=Revised subunit order of mammalian septin complexes explains their in vitro polymerization properties |journal=Molecular Biology of the Cell |date=2021 |volume=32 |issue=3 |pages=289–300 |doi=10.1091/mbc.E20-06-0398 |biorxiv=10.1101/569871|pmc=8098831}} in case of octameric hetero-oligomers). These complexes then associate to form non-polar filaments, filament bundles, cages or ring structures in cells. ==Occurrence== Septins are found in [fungi](/source/fungi), [animals](/source/animals), and some eukaryotic [algae](/source/algae) but are not found in plants. {| class="wikitable collapsible collapsed" border="1" |+ Septin genes in different exemplar species ! ! Species ! Group ([phylogenetic](/source/phylogenetic)) ! Septin genes |- | rowspan="17" | '''[Fungi](/source/Fungi)''' | rowspan="4" | ''[Saccharomyces cerevisiae](/source/Saccharomyces_cerevisiae)'' | Cdc3 || Cdc3 |- | Cdc10 || Cdc10 |- | Cdc11 || Cdc11, Shs1, Spr28 |- | Cdc12 || Cdc12, Spr3 |- | rowspan="4" | ''[Schizosaccharomyces pombe](/source/Schizosaccharomyces_pombe)'' | Spn1 || Spn1 |- | Spn2 || Spn2 |- | Spn3 || Spn3, Spn5, Spn7 |- | Spn4 || Spn4, Spn6 |- | rowspan="4" | ''[Candida albicans](/source/Candida_albicans)'' | Cdc3 || Cdc3 |- | Cdc10 || Cdc10 |- | Cdc11 || Cdc11, Sep7, Spr28 |- | Cdc12 || Cdc12, Spr3 |- | rowspan="5" | ''[Aspergillus nidulans](/source/Aspergillus_nidulans)'' | AspD || AspD |- | AspB || AspB |- | AspA || AspA |- | AspC || AspC |- | AspE || AspE |- | rowspan="6" | '''Animals''' | rowspan="4" | Humans | Sept2 || Sept1, Spet2, Sept4, Sept5 |- | Sept3 || Sept3, Sept9, Sept12 |- | Sept6 || Sept6, Sept8, Sept10, Sept11, Sept14 |- | Sept7 || Sept7 (Sept13 as a pseudogene) |- | rowspan="2" | ''[Caenorhabditis elegans](/source/Caenorhabditis_elegans)'' | UNC-59 || UNC-59 |- | UNC-61 || UNC-61 |- |} == In yeast == [[Image:S cerevisiae septins.jpg|thumb|right|250px|'''Septins in ''[Saccharomyces cerevisiae](/source/Saccharomyces_cerevisiae)'' '''(fluorescent micrograph)
• Green: septins (''AgSEP7-[GFP](/source/Green_fluorescent_protein)'')
• Red: cell outline ([phase contrast](/source/Phase_contrast_microscopy))
• Scale bar: 10 μm]] There are seven different septins in ''[Saccharomyces cerevisiae](/source/Saccharomyces_cerevisiae)''. Five of those are involved in mitosis, while two (Spr3 and Spr28) are specific to [sporulation](/source/sporulation). Mitotic septins (Cdc3, Cdc10, Cdc11, Cdc12, Shs1) form a ring structure at the bud neck during [cell division](/source/cell_division). They are involved in the selection of the bud-site, the positioning of the [mitotic spindle](/source/mitotic_spindle), polarized growth, and [cytokinesis](/source/cytokinesis). The sporulating septins (Spr3, Spr28) localize together with Cdc3 and Cdc11 to the edges of prospore membranes. ===Organization=== Septins form a specialised region in the cell cortex known as the septin cortex.{{cite journal |last1=Gladfelter |first1=AS |last2=Pringle |first2=JR |last3=Lew |first3=DJ |title=The septin cortex at the yeast mother-bud neck. |journal=Current Opinion in Microbiology |date=December 2001 |volume=4 |issue=6 |pages=681–9 |pmid=11731320 |doi=10.1016/s1369-5274(01)00269-7}} The septin cortex undergoes several changes throughout the [cell cycle](/source/cell_cycle): The first visible septin structure is a distinct ring which appears ~15 min before [bud](/source/budding) emergence. After [bud](/source/budding) emergence, the ring broadens to assume the shape of an [hourglass](/source/hourglass) around the mother-bud neck. During [cytokinesis](/source/cytokinesis), the septin cortex splits into a double ring which eventually disappears. How can the septin cortex undergo such dramatic changes, although some of its functions may require it to be a stable structure? [FRAP](/source/Fluorescence_recovery_after_photobleaching) analysis has revealed that the turnover of septins at the neck undergoes multiple changes during the [cell cycle](/source/cell_cycle). The predominant, functional conformation is characterized by a low turnover rate (frozen state), during which the septins are [phosphorylated](/source/Phosphorylation). Structural changes require a destabilization of the septin cortex (fluid state) induced by [dephosphorylation](/source/dephosphorylation) prior to [bud](/source/budding) emergence, ring splitting and [cell](/source/Cell_(biology)) separation. The composition of the septin cortex does not only vary throughout the [cell cycle](/source/cell_cycle) but also along the mother-bud axis. This polarity of the septin network allows concentration of some [protein](/source/protein)s primarily to the mother side of the neck, some to the center and others to the [bud](/source/budding) site. ===Functions=== ====Scaffold==== The septins act as a scaffold, recruiting many [protein](/source/protein)s. These protein complexes are involved in [cytokinesis](/source/cytokinesis), [chitin](/source/chitin) deposition, [cell](/source/cell_(biology)) polarity, [spore](/source/spore) formation, in the [morphogenesis](/source/morphogenesis) checkpoint, [spindle](/source/mitotic_spindle) alignment [checkpoint](/source/Cell_cycle_checkpoint) and bud site selection. ====Cytokinesis==== Budding yeast [cytokinesis](/source/cytokinesis) is driven through two septin dependent, redundant processes: recruitment and contraction of the [actomyosin ring](/source/actomyosin_ring) and formation of the [septum](/source/septum) by [vesicle](/source/Vesicle_(biology)) fusion with the [plasma membrane](/source/Cell_membrane). In contrast to septin [mutant](/source/mutant)s, disruption of one single pathway only leads to a delay in [cytokinesis](/source/cytokinesis), not complete failure of [cell division](/source/cell_division). Hence, the septins are predicted to act at the most upstream level of [cytokinesis](/source/cytokinesis). ====Cell polarity==== After the [isotropic](/source/Isotropy)-[apical](/source/Apical_membrane) switch in [budding yeast](/source/Saccharomyces_cerevisiae), [cortical](/source/Cortex_(anatomy)) components, supposedly of the [exocyst](/source/exocyst) and [polarisome](/source/polarisome), are delocalized from the apical pole to the entire [plasma membrane](/source/Cell_membrane) of the bud, but not the mother cell. The septin ring at the neck serves as a cortical barrier that prevents membrane [diffusion](/source/diffusion) of these factors between the two compartments. This asymmetric distribution is abolished in septin [mutant](/source/mutant)s. Some conditional septin [mutant](/source/mutant)s do not form [bud](/source/budding)s at their normal axial location. Moreover, the typical localization of some bud-site-selection factors in a double ring at the neck is lost or disturbed in these [mutant](/source/mutant)s. This indicates that the septins may serve as anchoring site for such factors in axially [budding](/source/budding) cells. == In filamentous fungi == Since their discovery in ''[S. cerevisiae](/source/Saccharomyces_cerevisiae),'' septin [homologues](/source/Homology_(biology)) have been found in other [eukaryotic](/source/eukaryotic) species, including [filamentous](/source/Hypha) [fungi](/source/Fungus). Septins in filamentous fungi display a variety of different shapes within single [cells](/source/Cell_(biology)), where they control aspects of filamentous [morphology](/source/morphology_(biology)).{{cite book |last1=Harris |first1=SD |title=Cell Polarity in Filamentous Fungi: Shaping the Mold |series=International Review of Cytology |date=2006 |volume=251 |pages=41–77 |doi=10.1016/S0074-7696(06)51002-2 |pmid=16939777|isbn=978-0-12-364655-2 }} ===''Candida albicans''=== The [genome](/source/genome) of ''[C. albicans](/source/Candida_albicans)'' encodes [homologues](/source/Homology_(biology)) to all ''[S. cerevisiae](/source/Saccharomyces_cerevisiae)'' septins. Without Cdc3 and Cdc12 genes ''Candida albicans'' cannot proliferate, other septins affect morphology and [chitin](/source/chitin) deposition, but are not essential. ''Candida albicans'' can display different morphologies of vegetative growth, which determines the appearance of septin structures. Newly forming [hyphae](/source/hyphae) form a septin ring at the base, Double rings form at sites of hyphal septation, and a septin cap forms at hyphal tips. Elongated septin-[filament](/source/Protein_filament)s encircle the spherical [chlamydospore](/source/chlamydospore)s. Double rings of septins at the septation site also bear growth polarity, with the growing tip ring disassembling, while the basal ring remaining intact. ===''Aspergillus nidulans''=== Five septins are found in ''[A. nidulans](/source/Aspergillus_nidulans)'' (AnAspAp, AnAspBp, AnAspCp, AnAspDp, AnAspEp). AnAspBp forms single rings at septation sites that eventually split into double rings. Additionally, AnAspBp forms a ring at sites of branch emergence which broadens into a band as the branch grows. Like in ''[C. albicans](/source/Candida_albicans),'' double rings reflect polarity of the [hypha](/source/hypha). In the case of ''Aspergillus nidulans'' polarity is conveyed by disassembly of the more basal ring (the ring further away from the hyphal growth tip), leaving the apical ring intact, potentially as a growth guidance cue. ===''Ashbya gossypii''=== [[Image:A gossypii septins.jpg|thumb|right|300px|'''Septins in ''[Ashbya gossypii](/source/Ashbya_gossypii)'' '''(fluorescent micrograph) • Green: septins (''AgSEP7-[GFP](/source/Green_fluorescent_protein)'')
• Red: cell outline ([phase contrast](/source/Phase_contrast_microscopy))
• Inlay: 3D reconstruction of a discontinuous septin ring
• Scale bars: 10 μm]] The ''[ascomycete](/source/ascomycete) [A. gossypii](/source/Ashbya_gossypii)'' possesses [homologues](/source/Homology_(biology)) to all ''[S. cerevisiae](/source/Saccharomyces_cerevisiae)'' septins, with one being duplicated (''AgCDC3, AgCDC10, AgCDC11A, AgCDC11B, AgCDC12, AgSEP7''). ''[In vivo](/source/In_vivo)'' studies of AgSep7p-[GFP](/source/Green_fluorescent_protein) have revealed that septins assemble into discontinuous [hyphal](/source/hyphal) rings close to growing tips and sites of branch formation, and into [asymmetric](/source/asymmetry) structures at the base of branching points. Rings are made of [filament](/source/Protein_filament)s which are long and diffuse close to growing tips and short and compact further away from the tip. During [septum](/source/septum_(cell_biology)) formation, the [septin ring](/source/septin_ring) splits into two to form a double ring. ''Agcdc3Δ, Agcdc10Δ ''and ''Agcdc12Δ ''deletion [mutant](/source/mutant)s display aberrant [morphology](/source/Morphology_(biology)) and are defective for [actin](/source/actin)-ring formation, [chitin](/source/chitin)-ring formation, and [sporulation](/source/sporulation). Due to the lack of [septa](/source/Septum), septin deletion [mutant](/source/mutant)s are highly sensitive, and damage of a single [hypha](/source/hypha) can result in complete [lysis](/source/lysis) of a young [mycelium](/source/mycelium). == In animals == In contrast to septins in [yeast](/source/yeast), and in contrast to other [cytoskeletal](/source/cytoskeleton) components of animals, septins do not form a continuous network in cells, but several dispersed ones in the [cytoplasm](/source/cytoplasm) of the [cell cortex](/source/cell_cortex). These are integrated with [actin](/source/actin) bundles and [microtubules](/source/microtubules). For example, the actin bundling protein anillin is required for correct spatial control of septin organization. In the [sperm cells](/source/sperm) of [mammal](/source/mammal)s, septins form a stable ring called annulus in the tail. In mice (and potentially in humans, too), defective annulus formation leads to male infertility. === Human === In humans, septins are involved in [cytokinesis](/source/cytokinesis), [cilium](/source/cilium) formation and [neurogenesis](/source/neurogenesis) through the capability to recruit other proteins or serve as a diffusion barrier. There are 13 different human genes coding for septins. The septin proteins produced by these genes are grouped into four subfamilies each named after its founding member: (i) [SEPT2](/source/SEPT2) ([SEPT1](/source/SEPT1), [SEPT4](/source/SEPT4), [SEPT5](/source/SEPT5)), (ii) [SEPT3](/source/SEPT3) ([SEPT9](/source/SEPT9), [SEPT12](/source/SEPT12)), (iii) [SEPT6](/source/SEPT6) ([SEPT8](/source/SEPT8), [SEPT10](/source/SEPT10), [SEPT11](/source/SEPT11), [SEPT14](/source/SEPT14)), and (iv) [SEPT7](/source/SEPT7). Septin protein complexes are assembled to form either hetero-[hexamer](/source/hexamer)s (incorporating monomers selected from three different groups and the monomer from each group is present in two copies; 3 x 2 = 6) or hetero-[octamer](/source/octamer)s (monomers from four different groups, each monomer present in two copies; 4 x 2 = 8). These hetero-oligomers in turn form higher-order structures such as filaments and rings.{{cite journal |last1=Neubauer |first1=K |last2=Zieger |first2=B |title=The Mammalian Septin Interactome. |journal=Frontiers in Cell and Developmental Biology |date=2017 |volume=5 |page=3 |doi=10.3389/fcell.2017.00003 |pmid=28224124|pmc=5293755 |doi-access=free }} Septins form cage-like structures around [bacteria](/source/bacteria)l [pathogen](/source/pathogen)s, immobilizing harmful [microbe](/source/microbe)s and preventing them from invading healthy cells. This cellular defence system could potentially be exploited to create therapies for [dysentery](/source/dysentery) and other [illness](/source/illness)es. For example, ''[Shigella](/source/Shigella)'' is a [bacterium](/source/bacterium) that causes lethal [diarrhoea](/source/diarrhoea) in humans. To propagate from cell to cell, ''Shigella'' bacteria develop [actin](/source/actin)-[polymer](/source/polymer) 'tails', which propel the microbes and allow them to gain entry into neighbouring host cells. As part of the immune response, human cells produce a cell-signalling protein called [TNF-α](/source/TNF-%CE%B1) which trigger thick bundles of septin filaments to encircle the microbes within the infected host cell.{{cite journal | vauthors = Mostowy S, Bonazzi M, Hamon MA, Tham TN, Mallet A, Lelek M, Gouin E, Demangel C, Brosch R, Zimmer C, Sartori A, Kinoshita M, Lecuit M, Cossart P | title = Entrapment of intracytosolic bacteria by septin cage-like structures | journal = Cell Host Microbe | volume = 8 | issue = 5 | pages = 433–44 | year = 2010 | pmid = 21075354 | doi = 10.1016/j.chom.2010.10.009 | doi-access = free }} Microbes that become trapped in these septin cages are broken down by [autophagy](/source/autophagy).{{cite journal | vauthors = Mostowy S, [Sancho-Shimizu V](/source/Vanessa_Sancho-Shimizu), Hamon MA, Simeone R, Brosch R, Johansen T, Cossart P | title = p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways | journal = J. Biol. Chem. | volume = 286 | issue = 30 | pages = 26987–95 | year = 2011 | pmid = 21646350 | pmc = 3143657 | doi = 10.1074/jbc.M111.223610 | doi-access = free }} Disruptions in septins and [mutation](/source/mutation)s in the [gene](/source/gene)s that code for them could be involved in causing [leukaemia](/source/leukaemia), [colon cancer](/source/colon_cancer) and neurodegenerative conditions such as [Parkinson's disease](/source/Parkinson's_disease) and [Alzheimer's disease](/source/Alzheimer's_disease). Potential therapies for these, as well as for bacterial conditions such as dysentery caused by ''Shigella'', might bolster the body's [immune system](/source/immune_system) with [drug](/source/drug)s that mimic the behaviour of TNF-α and allow the septin cages to proliferate. === ''Caenorhabditis elegans'' === In the nematode worm ''[Caenorhabditis elegans](/source/Caenorhabditis_elegans)'' there are two [gene](/source/gene)s coding for septins, and septin complexes contain the two different septins in a tetrameric UNC59-UNC61-UNC61-UNC59 complex. Septins in ''C.elegans'' concentrate at the [cleavage furrow](/source/cleavage_furrow) and the [spindle midbody](/source/Midbody_(cell_biology)) during [cell division](/source/cell_division). Septins are also involved in cell migration and axon guidance in ''C.elegans''. ==In mitochondria== The septin localized in the [mitochondria](/source/mitochondria) is called mitochondrial septin (M-septin). It was identified as a [CRMP](/source/Collapsin_response_mediator_protein_family)/CRAM-interacting protein in the developing rat brain.{{cite journal | vauthors = Takahashi S, Inatome R, Yamamura H, Yanagi S | title = Isolation and expression of a novel mitochondrial septin that interacts with CRMP/CRAM in the developing neurones | journal = Genes Cells | volume = 8 | issue = 2 | pages = 81–93 | date = February 2003 | pmid = 12581152 | doi = 10.1046/j.1365-2443.2003.00617.x | doi-access = free }} ==History== The septins were discovered in 1970 by [Leland H. Hartwell](/source/Leland_H._Hartwell) and colleagues in a screen for temperature-sensitive [mutant](/source/mutant)s affecting [cell division](/source/cell_cycle) (cdc mutants) in yeast (''[Saccharomyces cerevisiae](/source/Saccharomyces_cerevisiae)''). The screen revealed four mutants which prevented [cytokinesis](/source/cytokinesis) at restrictive temperature. The corresponding [gene](/source/gene)s represent the four original septins, ''ScCDC3, ScCDC10, ScCDC11,'' and ''ScCDC12''. Despite disrupted cytokinesis, the [cells](/source/Cell_(biology)) continued [budding](/source/budding), [DNA synthesis](/source/DNA_replication), and [nuclear division](/source/mitosis), which resulted in large [multinucleate](/source/multinucleate) cells with multiple, elongated buds. In 1976, analysis of electron [micrograph](/source/micrograph)s revealed ~20 evenly spaced [striation](/source/%3Awikt%3Astriation)s of 10-nm [filament](/source/Protein_filament)s around the mother-bud neck in wild-type but not in septin-mutant cells.{{cite journal | vauthors = Gladfelter AS | title = Control of filamentous fungal cell shape by septins and formins | journal = Nat. Rev. Microbiol. | volume = 4 | issue = 3 | pages = 223–9 | year = 2006 | pmid = 16429163 | doi = 10.1038/nrmicro1345 | s2cid = 40080522 }} [Immunofluorescence](/source/Immunofluorescence) studies revealed that the septin [protein](/source/protein)s [colocalize](/source/colocalization) into a septin ring at the neck. The localization of all four septins is disrupted in conditional ''Sccdc3'' and ''Sccdc12'' mutants, indicating interdependence of the septin proteins. Strong support for this finding was provided by [biochemical](/source/Biochemistry) studies: The four original septins [co-purified](/source/List_of_purification_methods_in_chemistry) on [affinity column](/source/Affinity_chromatography)s, together with a fifth septin protein, encoded by ''ScSEP7'' or ''ScSHS1''. [Purified](/source/List_of_purification_methods_in_chemistry) septins from budding yeast, [Drosophila](/source/Drosophila), [Xenopus](/source/Xenopus), and [mammal](/source/mammal)ian cells are able to self associate ''[in vitro](/source/in_vitro)'' to form filaments. How the septins interact ''in vitro'' to form [hetero-oligomers](/source/Polymer) that assemble into filaments was studied in detail in ''S. cerevisiae''. Micrographs of purified filaments raised the possibility that the septins are organized in parallel to the mother-bud axis. The 10-nm striations seen on electron micrographs may be the result of lateral interaction between the filaments. Mutant strains lacking factors important for septin organization support this view. Instead of continuous rings, the septins form bars oriented along the mother-bud axis in deletion mutants of ''ScGIN4, ScNAP1'' and ''ScCLA4''. == References == {{Reflist|35em}} == Further reading == {{Refbegin|35em}} * {{cite journal | vauthors = Güler GÖ, Mostowy S | title = The septin cytoskeleton: Heteromer composition defines filament function | journal = The Journal of Cell Biology | volume = 222 | issue = 3 | article-number = e202302010 | date = Mar 2023 | pmid = 36821087 | doi = 10.1083/jcb.202302010 | pmc = 9998967 | doi-access = free }} * {{cite journal | vauthors = Longtine MS, DeMarini DJ, Valencik ML, Al-Awar OS, Fares H, De Virgilio C, Pringle JR | title = The septins: roles in cytokinesis and other processes | journal = Curr. Opin. Cell Biol. | volume = 8 | issue = 1 | pages = 106–19 | date = February 1996 | pmid = 8791410 | doi = 10.1016/S0955-0674(96)80054-8 | doi-access = free }} * {{cite journal | vauthors = Faty M, Fink M, Barral Y | title = Septins: a ring to part mother and daughter | journal = Curr. Genet. | volume = 41 | issue = 3 | pages = 123–31 | date = June 2002 | pmid = 12111093 | doi = 10.1007/s00294-002-0304-0 | s2cid = 22744214 }} * {{cite journal | vauthors = Versele M, Gullbrand B, Shulewitz MJ, Cid VJ, Bahmanyar S, Chen RE, Barth P, Alber T, Thorner J | title = Protein-protein interactions governing septin heteropentamer assembly and septin filament organization in Saccharomyces cerevisiae | journal = Mol. Biol. Cell | volume = 15 | issue = 10 | pages = 4568–83 | date = October 2004 | pmid = 15282341 | pmc = 519150 | doi = 10.1091/mbc.E04-04-0330 }} * {{cite journal | vauthors = Douglas LM, Alvarez FJ, McCreary C, Konopka JB | title = Septin function in yeast model systems and pathogenic fungi | journal = Eukaryotic Cell | volume = 4 | issue = 9 | pages = 1503–12 | date = September 2005 | pmid = 16151244 | pmc = 1214204 | doi = 10.1128/EC.4.9.1503-1512.2005 }} * {{cite journal | vauthors = Gladfelter AS | title = Control of filamentous fungal cell shape by septins and formins | journal = Nat. Rev. Microbiol. | volume = 4 | issue = 3 | pages = 223–9 | date = March 2006 | pmid = 16429163 | doi = 10.1038/nrmicro1345 | s2cid = 40080522 }} * {{cite thesis|author=Castro-Linares G | title = The septin circus: An Unforgettable Show of Cellular Choreography | publisher = TU Delft | location = Delft | year = 2023 | page = 302 | isbn = 978-94-6384-491-8 }} * {{cite book |author1=Hall PA |author2=Russell SEH |author3=Pringle JR | title = The septins | publisher = John Wiley-Blackwell | location = Oxford | year = 2008 | page = 370 | isbn = 978-0-470-51969-1 }} *{{cite journal |author1=Gonzalez-Novo A |author2=Vázquez de Aldana CR |author3=Jimenez J | title = Fungal septins: one ring to rule it all? | journal = Cent. Eur. J. Biol. | volume = 4 | issue = 3 | pages = 274–289 | year = 2009 | doi = 10.2478/s11535-009-0032-2 | doi-access = free | hdl = 10261/66544 | hdl-access = free }} {{refend}} Category:Cell biology Category:Cell cycle Category:Proteins Category:Cellular processes Category:Cytoskeleton --- Adapted from the Wikipedia article [Septin](https://en.wikipedia.org/wiki/Septin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Septin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.