Biology subjects

Bertin, A.

Publications and source records attributed to Bertin, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Reconstruction of septin higher-order nano-size structures in ovarian cancer cells uncover susceptibility to the septin-targeting small molecule UR214-9

In cancer cells, septins assemble into enigmatic higher-order structures of 300-700 nanometers, including long needle-like filaments, thick perinuclear rings, and cytoplasmic bundles or aggregates. The absence of genetic or pharmacological tools to recapitulate these architectures in-vitro has impeded mechanistic studies of their formation, function, and therapeutic targeting. Here, first, determining the overexpression of septin-2 in epithelial ovarian cancer (EOC) and its association with increased mortalities and dependencies, we select SKOV-3 ovarian cancer cells as a tractable model in which septin supramolecular assemblies can be recreated in-vitro and interrogated. This system shows that the forchlorfenuron (FCF) analog UR214-9 remodels septin architecture, converting co-expressed human septin octamers (SEPT2-SEPT6-SEPT7-SEPT9-SEPT9-SEPT7-SEPT6-SEPT2) into large cytoplasmic aggregates. In parallel, transiently expressed SEPT2 is reorganized into septin-rich noodle-like filaments, perinuclear rings, and web-like networks encircling the nucleus upon UR214-9 treatment. Mechanistically, UR214-9 disrupts the incorporation of SEPT2, SEPT7, and SEPT9 into canonical septin hetero-octamers, resulting in assembly-defective or imperfect oligomers that preferentially reorganize into these aberrant higher-order structures. This aggregation likely prevents septin-2 migration during interphase-to-cleavage furrow transition in NRK-49F-SEPT2-EGFP homozygous cells and impacts SKOV-3 cytokinesis, cell proliferation, adhesion and invasion and migration while sparing ceramide transport to the Golgi, preserving ER and cis-Golgi structure. These effects manifested in reduced growth of ovarian, endometrial and breast cancer xenografts without attracting significant off-target engagements per the global transcriptomic analysis of JIMT1 breast cancer and PANC-1 pancreatic cells. UR214-9 treated animals showed observable safety in animals. Thus, a tool to recreate aberrant septin structures and identification of septins as a druggable cytoskeletal target for ovarian, endometrial, breast and pancreatic cancer by perturbing their hetero-octamerization assembly is presented. SignificanceWe provide a method to reconstruct the higher-order septin architecture observed in cancer cells, to study their assembly and functions. Intriguingly, cancer cells tolerate hetero-oligomeric septins lacking specific subunits, suggesting that compositionally deficient oligomers are not efficiently targeted for degradation, unlike unincorporated septin monomers in normal cells. This tolerance may enable accumulation of structurally aberrant septin complexes acquiring long-needles, rings or thick-aggregates in disease cells. We further show that septin oligomerization can be pharmacologically perturbed. By integrating structural, cellular, and energetic readouts using in-silico techniques, we establish a quantitative framework for septin-targeted modulation, generating UR214-9 as a new chemotype that disrupts septin oligomeric assembly via preventing incorporation of SEPT2/7/9, into canonical hetero-octamers, causes defects in cytokinesis, altered cell migration, viability, and remodels septin-actin architectures, ultimately impairing tumor cell growth. Thus, pharmacological targeting of septin assembly represents a tractable strategy to perturb septin-dependent cellular processes in cancer and neurodegenerative diseases with reported septin dysregulation.

cancer biology↗

bioRxiv2026

Unexpected softening of giant unilamellar vesicles by budding yeast septin filaments: a curvature dependent mechanism

Budding yeast septins assemble into filamentous networks bound to the inner plasma membrane. In situ or in vitro, septins are implicated in membrane deformations. We therefore suspected that septins might alter membrane mechanical properties both directly or indirectly. To decipher whether septins directly tune the rigidity of membranes, we used a cell free in vitro approach. To this end, using AFM, we measured the mechanical response of reconstituted GUVs pre-incubated with septins. Unexpectedly, we find that large GUVs (typically tens of {micro}m diameter size) are more deformable in the presence of septins. Theoretical modeling suggests that this peculiar behavior is likely due to initial micrometer membrane "wrinkled" deformations imposed by septins. Conversely, small GUVs (1 to 2 microns in diameter) cannot undergo any micrometric deformations and are thereby less deformable with septin filaments bound. Our findings suggest that, in specific cellular context, septins could provide a membrane reservoir and eventually facilitate membrane deformations. Significance statementFilamentous cytoskeletal septins, interacting with membranes would be expected to enhance membrane rigidity. Upon mechanical stress, GUVs larger than tens of microns appear, more deformable in the presence of septins. Septins initial membrane reshaping is responsible for this unexpected behavior, as shown by theoretical modeling. However smaller non deformable vesicles are more rigid, with septins bound.

biophysics↗

bioRxiv2026

Diffusion Probabilistic Models for Missing-Wedge Correction in Cryo-Electron Tomography

Interpretation of 3D cryo-electron tomography (cryo-ET) reconstructions (tomograms) is hampered by the so-called missing-wedge (MW) distortions, which arise because tilt image series used for the reconstructions are acquired in a limited angular range. While many deep-learning approaches address the correction of the MW artifacts on the level of tomograms (3D volumes), the correction at the level of 2D tilt images (generation of unacquired images) remains underexplored. We propose MW-RaMViD, a 2D tilt-image generation method for MW correction, based on Random-Mask Video Diffusion (RaMViD) method for prediction of frames in natural videos. To adapt RaMViD for cryo-ET, we add MRC image-format support, floating-point pixel intensity representation, and a controlled inference protocol enabling both one-run and progressive MW completion (generating a small number of missing tilts per step using a sliding window). We evaluate the method on a synthetic noisy tilt-series dataset and study the effects of MW completion step size and conditioning sequence length. Results show that smaller step sizes and larger conditioning windows reduce error accumulation at higher tilt angles and improve reconstruction fidelity, which was measured by Root Mean Square Error on the image level and by Fourier Shell Correlation on the tomogram level.

bioinformatics↗

bioRxiv2025

Septin Architecture Dictates Size-Dependent Diffusion Barriers on biomimetic Membranes

Septins are cytoskeletal filaments bound to the inner leaflet of the plasma membrane, essential for cell division. They are involved in the formation of diffusion barriers for membrane-bound components. Whether septins directly function as barriers or as part of a broader regulatory cascade of events remains unclear. We addressed this using in vitro reconstituted assay of biomimetic synthetic membranes. We probed whether the diffusion of biomimetic fluorescent objects with tunable steric hindrance - mimicking membrane bound proteins - is constrained by septins. Our results indicate that (i) lipids and transmembrane proteins lacking cytosolic domains diffuse freely in the presence of septins (ii) membrane-bound objects with large cytosolic domains experience size-dependent diffusion constraints; and (iii) the ability of septins to act as diffusion barriers is finely tuned by their intrinsic filament organization. These findings demonstrate that septins can directly impose size-selective diffusion barriers and that their filament organization critically tunes this function.

biophysics↗

bioRxiv2025

Architecture and function of Bud3 and Bud4-induced septin structures

At the time of cytokinesis, a double septin ring is assembled at the division site in many eukaryotic cells. In budding yeast the double ring is made by two arrays of circumferential septin filaments at the two sides of the bud neck, which are thought to compartmentalize the membrane around the cleavage site. Integrity of the double septin ring requires the anillin Bud4 and its presumed partner Bud3, which associate with septins in mitosis and have separate, yet unknown, roles in stabilizing septin circumferential filaments. Through in vitro reconstitution assays using purified proteins, we show that Bud3 and Bud4 organise septin filaments in distinct ways, while together they cooperate to assemble higher-order septin networks. In agreement with their separate roles in septin organization, Bud3 and Bud4 bind to different septins and require septins to associate with each other, indicating that they modulate septin architecture independently but synergistically. We also provide evidence that Bud3 and Bud4 bind membranes in vivo and in vitro, consistent with the presence of lipid-binding domains in their primary sequence. Using bud3 bud4 double mutants that lack the septin double ring, we show that in vivo proteins marking cytokinetic remnants require the double ring to efficiently concentrate at the division site, while other proteins landing at the bud neck at cytokinesis are unaffected. Thus, we propose that a septin double ring may imprint a selective spatial memory for cytokinesis that is transmitted throughout subsequent cell divisions.

cell biology↗

bioRxiv2025

The PXBAR-domain protein SNX9 selectively sequesters PI(3,4)P2 lipid and protects it from hydrolysis at the plasma membrane

Plasma membrane remodeling processes are tightly regulated by the spatiotemporal distribution and dynamic conversion of phosphoinositidyl lipids (PIPs). This regulation is controlled by the recruitment of proteins such as sorting nexin 9 (SNX9), a key mediator of late-stage endocytosis and macropinocytosis. Using live cell imaging, in vitro reconstitution assays, and molecular dynamics simulations, we investigated how SNX9 distinguishes between PI(3,4)P2 and PI(4,5)P2, and the physiological relevance of this selectivity. Our results revealed that during macropinocytic membrane ruffling, SNX9 is recruited in a spatiotemporally coordinated manner with PI(3,4)P2, but not with PI(4,5)P2. While SNX9 induces comparably weak mechanical remodeling on model membranes containing either PIP2 species, it exhibits a clear selective binding to PI(3,4)P2, mediated by a non-canonical interface. Through mutational analysis of key residues involved in this sequestration, we further demonstrated that SNX9 protects PI(3,4)P2 from hydrolysis. Together, these results reveal a previously unrecognized mechanism of SNX9-PIP2 lipid interaction that underscores SNX9s pivotal role in coordinating membrane remodeling processes. TeaserCurvature sensing BAR protein SNX9 selectively sequesters PI(3,4)P2 lipids, acting as a checkpoint in cell membrane remodeling.

biophysics↗

bioRxiv2023

On-farm hatching and contact with adult hen post hatch induce sex-dependent effects on performance and welfare in broiler chickens

To improve the early perinatal conditions of broiler chicks, alternative hatching systems have been developed. On-farm hatching (OFH) with an enriched microbial and stimulating environment by the presence of an adult hen is a promising solution. Day-old chicks were allotted within five hatching and rearing conditions: OFH, conventional hatchery (CH), CH and post-hatching treatment with antibiotics (CH + AB), as well as both hatching systems with an adult hen at hatching (OFH + H, CH + H). To challenge the robustness of chickens, they were exposed on D27 to suboptimal rearing conditions by combining for 4 h transport in boxes in a new room at a lower temperature and fasting. On their return to the original room, the chicken density was increased, and birds were orally vaccinated with the Gumboro vaccine. The impacts of these conditions on hatchability, chick quality score, performance, health and robustness were determined. The OFH chick body weights (BWs) were significantly greater than those of CH chicks at hatching. Whereas there was no effect of hatching conditions, the presence of hens decreased the hatchability rate, the quality score of OFH chicks and increased mortality at hatching. Treatment of CH chicks with antibiotics (CH + AB) temporarily decreased chicken BW at D19, but the feed conversion ratio (FCR) was not modified. At D19, OFH chicks had the highest BW compared to the other groups, and the presence of hens at hatching harmed chicken BW regardless of the hatching condition and FCR. An interaction between the effect of experimental rearing conditions and chicken sex was observed later for BW. In males, the OFH chickens were the heaviest compared to the other groups at D34 but not at D56. The presence of hens negatively impacted CH chicken BW at D56. In females, there was no effect of hatching condition on the BWs at D34 and D56, and the presence of hens had a positive impact on OFH chicken BW. There was no effect of hatching conditions on health parameters. In conclusion, the OFH system was a hatching system at least equivalent to the CH system. The presence of the hen at hatching and during the chick start-up phase on performance interacted with the hatching condition and the sex of the chickens.

physiology↗

bioRxiv2022

A specific mesh-like organization of human septin octameric complex drives membrane reshaping and curvature sensitivity

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane, we have used a combination of methods to assay their ultrastructural organization, their curvature sensitivity as well as their role in membrane reshaping. In contrast to budding yeast septins, on membranes, human septins systematically organize into a two-layered mesh of orthogonal filaments instead of generating parallel sheets of filaments observed for budding yeast septins. This peculiar mesh organization is curvature sensitive and drives membrane reshaping as well. The observed membrane deformations together with the filamentous organization are recapitulated in a coarsegrained computed simulation to understand their mechanisms. Our results highlight the specificity of animal septins as opposed to fungal proteins.

biophysics↗

bioRxiv2022

Polymerization cycle of actin homolog MreB from a Gram-positive bacterium

In most rod-shaped bacteria, the actin homologue MreB is an essential component of the protein complex effecting cell wall elongation. The polymerization cycle and filament properties of eukaryotic actin have studied for decades and are well characterized. However, purification and in vitro work on MreB proteins have proven very difficult. Current knowledge of MreB biochemical and polymerization properties remains limited and is based on MreB proteins from Gram-negative species. In this study, we report the first observation of organized filaments and the first 3D-structure of MreB from a Gram-positive bacterium. We have purified MreB from the thermophilic Geobacillus stearothermophilus and shown that it forms straight pairs of protofilaments in vitro, and that polymerization depends on the presence of both lipids and nucleotide triphosphate. Two spatially close short hydrophobic sequences mediate membrane anchoring. Importantly, we demonstrate that unlike eukaryotic actin, nucleotide hydrolysis is a prerequisite for MreB interaction with the membrane, and that binding to lipids then triggers polymerization. Based on our results, we propose a molecular model for the mechanism of MreB polymerization.

biochemistry↗

bioRxiv2022

Direct observation of the conformational states of formin mDia1 at actin filament barbed ends and along the filament.

The fine regulation of actin polymerization is essential to control cell motility, architecture and to perform essential cellular functions. Formins are key regulators of actin filament assembly, known to processively elongate filament barbed ends and increase their polymerization rate. Based on indirect observations, different models have been proposed to describe the molecular mechanism governing the processive motion of formin FH2 domains at polymerizing barbed ends. Using electron microscopy, we directly identified two conformations of the mDia1 formin FH2 domains in interaction with the barbed ends of actin filaments. These conformations agree with the open and closed conformations of the "stair stepping" model proposed by Otomo and colleagues1. We observed the FH2 dimers to be in the open conformation for 79% of the data, interacting with the two terminal actin subunits of the barbed end, while they interact with three actin subunits in the closed conformation. Further, our data reveal that the open state encompasses a continuum of states where the orientation of the leading FH2 domain with respect to the filament long axis varies from 108 to 135 degrees. In addition, we identified FH2 domains encircling the core of actin filaments, providing structural information for mDia1 away from the barbed end. Based on these direct observations, we propose a model of formin in interaction with the growing filament end, as well as with the core of the filament.

biophysics↗

bioRxiv2021

Landscape connectivity alters the evolution of density-dependent dispersal during pushed range expansions

AO_SCPLOWBSTRACTC_SCPLOWAs human influence reshapes communities worldwide, many species expand or shift their ranges as a result, with extensive consequences across levels of biological organization. Range expansions can be ranked on a continuum going from pulled dynamics, in which low-density edge populations provide the "fuel" for the advance, to pushed dynamics in which high-density rear populations "push" the expansion forward. While theory suggests that evolution during range expansions could lead pushed expansions to become pulled with time, empirical comparisons of phenotypic divergence in pushed vs. pulled contexts are lacking. In a previous experiment using Trichogramma brassicae wasps as a model, we showed that expansions were more pushed when connectivity was lower. Here we used descendants from these experimental landscapes to look at how the range expansion process and connectivity interact to shape phenotypic evolution. Interestingly, we found no clear and consistent phenotypic shifts, whether along expansion gradients or between reference and low connectivity replicates, when we focused on low-density trait expression. However, we found evidence of changes in density-dependence, in particular regarding dispersal: populations went from positive to negative density-dependent dispersal at the expansion edge, but only when connectivity was high. As positive density-dependent dispersal leads to pushed expansions, our results confirm predictions that evolution during range expansions may lead pushed expansions to become pulled, but add nuance by showing landscape conditions may slow down or cancel this process. This shows we need to jointly consider evolution and landscape context to accurately predict range expansion dynamics and their consequences.

ecology↗

bioRxiv2021

Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms

Septin GTP-binding proteins contribute essential biological functions that range from the establishment of cell polarity to animal tissue morphogenesis. Human septins in cells form hetero-octameric septin complexes containing the ubiquitously expressed SEPT9. Despite the established role of SEPT9 in mammalian development and human pathophysiology, biochemical and biophysical studies have relied on monomeric SEPT9 thus not recapitulating its native assembly into hetero-octameric complexes. We established a protocol that enabled the first-time isolation of recombinant human septin octamers containing distinct SEPT9 isoforms. A combination of biochemical and biophysical assays confirmed the octameric nature of the isolated complexes in solution. Reconstitution studies showed that octamers with either a long or a short SEPT9 isoform form filament assemblies, and can directly bind and cross-link actin filaments, raising the possibility that septin-decorated actin structures in cells reflect direct actin-septin interactions. Recombinant SEPT9-containing octamers will make it possible to design cell-free assays to dissect the complex interactions of septins with cell membranes and the actin/microtubule cytoskeleton. SummaryHuman septins in cells form hetero-octameric complexes containing the ubiquitously expressed SEPT9. Iv et al. describe the first-time isolation of recombinant human septin octamers with distinct SEPT9 isoforms. Reconstitution studies show that octamers with either a long or a short SEPT9 isoform form higher-order filament assemblies and directly bind and cross-link actin filaments.

cell biology↗

bioRxiv2021

Training level reveals a dynamic dialogue between stress and memory systems in birds

It is now well-accepted that memory is a dynamic process, and that stress and training level may influence which memory system an individual engages when solving a task. In this work, we investigated whether and how chronic stress impacts spatial and cue-based memories according to training level. To that aim, control and chronically stressed Japanese quail were trained in a task that could be solved using spatial and cue-based memory and tested for their memory performances after 5 and 15 training days (initial training and overtraining, respectively) and following an emotional challenge (exposure to an open field). While chronic stress negatively impacted spatial memory in chronically stressed birds after initial training, this impact was lowered after overtraining compared to control quail. Interestingly, the emotional challenge reinstated the differences in performance between the two groups, revealing that chronic stress/overtraining did not eliminate spatial memory. Differences caused by previous stressors can re-emerge depending on the more immediate psychological state of the individual. Contrary to spatial memory, cue-based memory was not impaired in any test occasion, confirming that this form of memory is resistant to chronic stress. Altogether these findings reveal a dynamic dialogue between stress, training, and memory systems in birds.

animal behavior and cognition↗

bioRxiv2020

Membrane binding controls ordered self-assembly of animal septins

Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here we show by cell-free reconstitution that membrane binding requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septins form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12 to 18 nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4 nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.

cell biology↗

bioRxiv2020

Shifts from pulled to pushed range expansions caused by reductions in connectedness

AO_SCPLOWBSTRACTC_SCPLOWRange expansions are key processes shaping the distribution of species; their ecological and evolutionary dynamics have become especially relevant today, as human influence reshapes ecosystems worldwide. Many attempts to explain and predict range expansions assume, explicitly or implicitly, so-called "pulled" expansion dynamics, in which the low-density edge populations provide most of the "fuel" for the species advance. Some expansions, however, exhibit very different dynamics, with high-density populations behind the front "pushing" the expansion forward. These two types of expansions are predicted to have different effects on e.g. genetic diversity and habitat quality sensitivity. However, empirical studies are lacking due to the challenge of generating reliably pushed vs. pulled expansions in the laboratory, or discriminating them in the field. We here propose that manipulating the degree of connectivity among populations may prove a more generalizable way to create pushed expansions. We demonstrate this with individual-based simulations as well as replicated experimental range expansions (using the parasitoid wasp Trichogramma brassicae as model). By analyzing expansion velocities and neutral genetic diversity, we showed that reducing connectivity led to pushed dynamics. Low connectivity alone, i.e. without density-dependent dispersal, can only lead to "weakly pushed" expansions, where invasion speed conforms to pushed expectations, but the decline in genetic diversity does not. In empirical expansions however, low connectivity may in some cases also lead to adjustments to the dispersal-density function, recreating "classical" pushed expansions. In the current context of habitat loss and fragmentation, we need to better account for this relationship between connectivity and expansion regimes to successfully predict the ecological and evolutionary consequences of range expansions.

ecology↗

bioRxiv2020

Myosin 1b Flattens and Prunes Branched Actin Filaments.

Motile and morphological cellular processes require a spatially and temporally coordinated branched actin network that is controlled by the activity of various regulatory proteins including the Arp2/3 complex, profilin, cofilin and tropomyosin. We have previously reported that myosin 1b regulates the density of the actin network in the growth cone. Using in vitro F-actin gliding assays and total internal reflection fluorescence (TIRF) microscopy we show in this report that this molecular motor flattens the Arp2/3-dependent actin branches up to breaking them and reduces the probability to form new branches. This experiment reveals that myosin 1b can produce force sufficient enough to break up the Arp2/3-mediated actin junction. Together with the former in vivo studies, this work emphasizes the essential role played by myosins in the architecture and in the dynamics of actin networks in different cellular regions. Short summaryUsing in vitro F-actin gliding assays and total internal reflection fluorescence (TIRF) microscopy we show that myosin flattens the Arp2/3-dependent actin branches up to breaking them and reduces the probability to form new branches

biophysics↗

bioRxiv2019

Human ESCRT-III Polymers Assemble on Positively Curved Membranes and Induce Helical Membrane Tube Formation

Endosomal sorting complexes required for transport-III (ESCRT-III) are thought to assemble in vivo inside membrane structures with a negative Gaussian curvature. How membrane shape influences ESCRT-III polymerization and conversely how ESCRT-III polymers shape membranes is still unclear. Here, we used human core ESCRT-III proteins, CHMP4B, CHMP2A, CHMP2B and CHMP3 to address this issue in vitro by combining membrane nanotube pulling experiments, cryo-electron microscopy, cryo-electron tomography and high-speed AFM. We show that CHMP4B filaments bind preferentially to flat membranes or to membrane tubes with a positive mean curvature. Both CHMP2B and CHMP2A/CHMP3 assemble on positively curved membrane tubes, the latter winding around the tubes. Although combinations of CHMP4B/CHMP2B and CHMP4B/CHMP2A/CHMP3 are recruited to the neck of pulled membrane tubes, they also reshape large unilamellar vesicles into helical membrane tubes with a pipe surface shape. Sub-tomogram averaging reveals that the filaments assemble parallel to the tube axis with some local perpendicular connections, highlighting the particular mechanical stresses imposed by ESCRT-III to stabilize the corkscrew-like membrane architecture. Our results thus underline the versatile membrane remodeling activity of ESCRT-III that may be a general feature of ESCRT-III required for all or selected cellular membrane remodeling processes.

cell biology↗

bioRxiv2019

Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast

Septin proteins co-assemble into hetero-oligomers that polymerize into cytoskeletal filaments with a variety of cellular functions. In Saccharomyces cerevisiae, where septins were first discovered, five subunits comprise two species of septin hetero-octamers, Cdc11/Shs1-Cdc12-Cdc3-Cdc10- Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Septins evolved from ancestral GTPases. We previously found evidence that slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1 into septin complexes. It was unclear why many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that the small molecule guanidine hydrochloride (GdnHCl) rescues septin function in cdc10 mutants by promoting assembly of non-native Cdc11/Shs1-Cdc12-Cdc3- Cdc3-Cdc12-Cdc11/Shs1 hexamers. We provide evidence that in S. cerevisiae Cdc3 guanidinium ion (Gdm) occupies the site of a "missing" Arg sidechain that is present in other fungal species in which (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers co-exist with octamers in wild-type cells. These findings support a model in which Gdm reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to hetero-octamers. Given that septin hexamers made natively in human cells also exclude Cdc10-like central subunits via homodimerization of an active GTPase, our results provide new mechanistic details that likely apply to septin assembly throughout phylogeny.

genetics↗