Mastodawn

📰 "Septin-mediated coupling of protein import and division during chloroplast evolution"
https://www.biorxiv.org/content/10.64898/2026.03.28.715002v1?rss=1
#Septin

Septin-mediated coupling of protein import and division during chloroplast evolution

Chloroplast biogenesis depends on both protein import and organelle division, yet how their coordination emerged during evolution remains unclear. Here, we show that the single septin SEP1 links these pathways in the green alga Chlamydomonas reinhardtii . SEP1 forms a filamentous network on the chloroplast envelope during interphase and reorganizes into a ring at the chloroplast division site during cytokinesis. Loss of SEP1 selectively impairs import of chloroplast-division proteins and causes mispositioning of the division ring, without impairing bulk chloroplast protein import. SEP1 physically associates with outer-envelope TOC GTPases through evolutionarily related GTPase domains. Phylogenetic analysis places TOC GTPases within an algal septin-derived clade, and heterologous expression of SEP1 in land plants, in which septins are absent, shows conservation of its chloroplast targeting and TOC binding. Together, these findings identify septins as coordinators of plastid protein import and division and suggest that this coupling emerged early in chloroplast evolution. ### Competing Interest Statement The authors have declared no competing interest. U.S. National Science Foundation, 1818383, 2337141 Austrian Academy of Sciences FWF Austrian Science Fund, AST1678424 European Commission, 101078291 EMBL core support Duke University Trinity College of Arts & Sciences EMBO Young Investigator Programme Bielefeld Young Researchers' Fund National Institutes of Health, T32GM142605 Hung Taiwan-Duke University Fellowship Duke Biological Sciences Undergraduate Research Fellowship

bioRxiv

Rxiv cytoskeleton 5d ago

📰 "Curcumin delays cytokinesis in fission yeast by targeting the septin ring"
https://doi.org/doi:10.1242/jcs.264321
https://pubmed.ncbi.nlm.nih.gov/41891373/
#Septin

Curcumin delays cytokinesis in fission yeast by targeting the septin ring

Curcumin is the active compound of one of the most widely used spices in the world. It has also been highly valued as a traditional health supplement in many South Asian countries for millennia. More recently, this plant extracted small molecule has attracted strong attention for its therapeutic potential. Nevertheless, the molecular and cellular targets of curcumin remain unknown. Here, we undertook a novel imaging-based approach to determine the intracellular distribution of curcumin using the model organism fission yeast Schizosaccharomyces pombe by taking advantage of the intrinsic fluorescence of curcumin. Live fluorescence microscopy revealed for the first time that curcumin, at a concentration of just one micromolar, formed a narrow circumferential ring around the equatorial plane of dividing cells within minutes after being added to the yeast culture. The intensity of this ring increased proportionally to the concentration of curcumin and gradually over time. The curcumin ring co-localized both spatially and temporally with septin ring and the exocyst complex at the equatorial plane during cytokinesis. Deletion of one of the septin genes spn4 reduced the frequency of curcumin ring by 74%. Micromolar concentrations of curcumin slowed down the contractile ring constriction by up to 49% in a dosage dependent manner. Besides fission yeast, curcumin similarly targets the division plane of two other yeasts, Saccharomyces cerevisiae and Candida albicans. Thus, curcumin, originated from plants, targets the septin cytoskeleton to delay yeast cytokinesis, suggesting its potential as both an antifungal therapeutic option and a fluorescence probe for yeast septins.

The Company of Biologists

Rxiv cytoskeleton Mar 25

📰 "Local RhoA activation induces anillin-independent septin recruitment in interphase cells"
https://doi.org/doi:10.1091/mbc.E25-09-0468
https://pubmed.ncbi.nlm.nih.gov/41880215/
#Septin #Actin

Rxiv cytoskeleton Mar 11

📰 "Coiled-coil homo-oligomerization and disaggregase Hsp104 act in parallel to stabilize orphan septins"
https://www.biorxiv.org/content/10.64898/2026.03.09.710472v1?rss=1
#Septin

Rxiv cytoskeleton Mar 2

📰 "Septin Complexes Regulate Microtubule Organization and Synaptic Function at the Neuromuscular Junction"
https://www.biorxiv.org/content/10.64898/2026.03.01.708893v1?rss=1
#Microtubule #Septin

Septin Complexes Regulate Microtubule Organization and Synaptic Function at the Neuromuscular Junction

Septins are conserved filamentous GTP-binding proteins that assemble at membranes and cytoskeletal interfaces, yet how they organize neuronal architecture in vivo remains incompletely understood. In neurons, microtubule organization is central to polarity, transport, and synaptic function, but the contribution of septin complexes to microtubule-dependent synaptic architecture remains unclear. Using the genetically tractable and paralog-restricted septin system of Drosophila melanogaster, we dissect the roles of Sep2 and Sep5 at larval neuromuscular junctions. Through integrated genetic, behavioral, immunostaining, and transcriptomic analyses, we show that septin loss disrupts pre- and postsynaptic organization and vesicle recycling while altering microtubule architecture. Notably, loss of septins shifts microtubules toward an acetylated and stabilized state, accompanied by increased expression of microtubule-associated and stabilization-linked factors, including tau, among the most upregulated genes and ringmaker, consistent with enhanced microtubule stabilization. Together, these findings position septin complexes as structural organizers that buffer microtubule state to preserve synaptic architecture, establishing septin composition as a key determinant of neuronal cytoskeletal organization in vivo. ### Competing Interest Statement The authors have declared no competing interest. TEKFEN Foundation, Grant 22B1TFV1 Boğaziçi University Research Fund, Grant 23B01S2 TÜBİTAK, Grant 125Z805

bioRxiv

Rxiv cytoskeleton Feb 23

📰 "Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast"
https://doi.org/doi:10.64898/2026.02.13.705769
https://pubmed.ncbi.nlm.nih.gov/41726955/
#Septin

Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast

Adaptor protein complex 3 (AP-3) mediates clathrin-independent transport to lysosomes, yet accessory factors supporting this pathway remain incompletely defined. In Saccharomyces cerevisiae , the C-terminal intrinsically disordered regions (IDRs) of both AP-3 large subunits (δ and β3) serve as platforms for association with accessory factors. Through proteomic analysis of proteins associated with these IDRs, we identify the septin cytoskeleton as a candidate AP-3-associated factor. Bimolecular fluorescence complementation (BiFC) reveals a hierarchical pattern of association: AP-3 shows preferential proximity to core septin subunits (Cdc10, Cdc3, Cdc12) over terminal subunits (Cdc11 and Shs1). These terminal subunits serve as alternative caps of septin octamers, generating structurally distinct assemblies. Significantly, dysfunction of Cdc11 but not Shs1 selectively impairs AP-3-dependent cargo sorting without affecting the parallel vacuolar protein sorting (VPS) pathway to the vacuole (lysosome in yeast), providing genetic evidence for a specific functional connection between Cdc11-containing septin assemblies and AP-3-mediated transport. ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35 GM149202, R01 GM07749, R01 13064 Natural Sciences and Engineering Research Council, https://ror.org/01h531d29, RGPIN-2022-04573, RGPIN-2016-04290

bioRxiv

Rxiv cytoskeleton Feb 15

📰 "Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast"
https://www.biorxiv.org/content/10.64898/2026.02.13.705769v1?rss=1
#Septin

Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast

Adaptor protein complex 3 (AP-3) mediates clathrin-independent transport to lysosomes, yet accessory factors supporting this pathway remain incompletely defined. In Saccharomyces cerevisiae , the C-terminal intrinsically disordered regions (IDRs) of both AP-3 large subunits (δ and β3) serve as platforms for association with accessory factors. Through proteomic analysis of proteins associated with these IDRs, we identify the septin cytoskeleton as a candidate AP-3-associated factor. Bimolecular fluorescence complementation (BiFC) reveals a hierarchical pattern of association: AP-3 shows preferential proximity to core septin subunits (Cdc10, Cdc3, Cdc12) over terminal subunits (Cdc11 and Shs1). These terminal subunits serve as alternative caps of septin octamers, generating structurally distinct assemblies. Significantly, dysfunction of Cdc11 but not Shs1 selectively impairs AP-3-dependent cargo sorting without affecting the parallel vacuolar protein sorting (VPS) pathway to the vacuole (lysosome in yeast), providing genetic evidence for a specific functional connection between Cdc11-containing septin assemblies and AP-3-mediated transport. ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35 GM149202, R01 GM07749, R01 13064 Natural Sciences and Engineering Research Council, https://ror.org/01h531d29, RGPIN-2022-04573, RGPIN-2016-04290

bioRxiv

Rxiv cytoskeleton Feb 8

📰 "Local PI(4,5)P2 synthesis by septin-associated PIPKIγ isoforms controls centralspindlin association with the midbody during cytokinesis"
https://doi.org/doi:10.1038/s41467-026-69224-3
https://pubmed.ncbi.nlm.nih.gov/41654539/
#Actomyosin #Septin

Rxiv cytoskeleton Feb 6

📰 "Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress"
https://doi.org/doi:10.64898/2026.01.21.700789
https://pubmed.ncbi.nlm.nih.gov/41648557/
#Actomyosin #Septin

Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress

Invasively migrating cells thread their nucleus through confined interstitial spaces. How cells protect the nucleus from intracellular forces is poorly understood. Here, we show that the septin cytoskeleton buffers the actomyosin forces that power nuclear movement. Septin filaments comprising SEPT9, a septin amplified in breast cancer, align with perinuclear actomyosin cables which exhibit higher tensile stress during 3D confined migration through narrower pores. SEPT9 depletion amplifies actin stress during confined migration and after myosin II hyper-activation in non-migrating cells causing actin and nuclear envelope ruptures. Following confined migration, DNA breaks, nuclear blebs, micronuclei and cell death increase in SEPT9-depleted cells, phenotypes rescued by the oncogenic SEPT9 isoform 1. Clinicogenomic data reveal that SEPT9 amplification associates with lower genomic alteration in aggressive breast tumors and higher patient mortality. We propose that septins are a mechanoprotective element of the cytoskeleton, and SEPT9 amplification enhances tumor cell survival by preventing nuclear damage. ### Competing Interest Statement The authors have no competing interests. National Institute of General Medical Sciences, https://ror.org/04q48ey07, 2 R35GM136337-07 National Institute on Aging, https://ror.org/049v75w11, 4 R01AG068908-03

bioRxiv

Rxiv cytoskeleton Feb 6

📰 "Mechanically-induced Septin Networks Protect Nuclear Integrity"
https://doi.org/doi:10.64898/2026.01.20.700414
https://pubmed.ncbi.nlm.nih.gov/41648276/
#Cytoskeleton #Septin

Mechanically-induced Septin Networks Protect Nuclear Integrity

The cytoskeleton is a key mediator of mechanical interactions in cells, but specific contributions of septins remains unclear. Septins preferentially localize with a subset of actin stress fibers positioned under the nucleus, where they are situated between the membrane and stress fibers. Removing the nucleus from the cell results in the loss of these subnuclear septin-decorated stress fibers. Surprisingly, however, their formation can be rescued using a large glass bead in place of the nucleus. Similarly, applying a compressive force to the cell via confinement, whether externally or through internally generated actomyosin forces, results in increased septin accumulation in regions where the nucleus engages the cell cortex. Finally, loss of septin filaments via knockdown of SEPT7 increases the likelihood of nuclear membrane rupture during confinement. Together these data suggest that septins act as a dynamic mechanosensitive protective mechanism to buffer mechanical forces on the nucleus. ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R01-GM148644, R35-GM138183 U.S. National Science Foundation, 2000554

bioRxiv