Biology subjects

Cortes, D. B.

Publications and source records attributed to Cortes, D. B..

6 recordsLinked to original sources

bioRxiv2026

Organelle Volume Facilitates Spindle Positioning During C. elegans Female Meiosis

Cortical positioning of oocyte meiotic spindles is required for reducing chromosome number by segregating chromosomes into polar bodies. In C. elegans, kinesin-1 transports membrane-bound organelles inward into a central ball that is hypothesized to push the meiotic spindle outward. Using focused ion beam scanning electron microscopy, we found that the percent volume occupied by membrane-bound organelles was 28% in a mature oocyte that has completed endocytosis of the yolk precursor, vitellogenin, compared to 17% in a less mature oocyte that has not yet endocytosed vitellogenin. We therefore hypothesized that blocking endocytosis of vitellogenin would reduce the size of the central ball of organelles packed inward by kinesin-1 and limit outward movement of the spindle. Depletion of vitellogenin or proteins required for endocytosis resulted in a smaller central volume of kinesin-coated organelles and defective spindle positioning. A computer simulation of a simple exclusion model faithfully recapitulated wildtype and mutant spindle position phenotypes. These results support a volume exclusion model for positioning acentriolar meiotic spindles.

cell biology↗

bioRxiv2026

Discovery of new marine species Stentor hondawara and its whole-genome reveal their unique ecology in comparison with freshwater stentors

Stentor is a genus of large ciliates that can be found in ponds, lakes, rivers, and fresh waters all over the world. Since their initial discovery in 1744, Stentor strains have been isolated from all populated continents. To date, over 50 individual strains have been identified, yet not a single isolate from a marine environment has been verified. Over 200 years since the initial description of the Stentor genus, our study entails the first concrete discovery of a fully marine Stentor species, as evidenced by its morphological, ecological, and phylogenetic positioning amongst Stentor. This new marine organism, which we have named Stentor hondawara, was verified to be a new species of the Stentor genus that appears to have fully adapted to a uniquely marine lifestyle in a high-salinity environment. Using comparative genomics analysis between the whole-genome sequences of Stentor hondawara and two freshwater species of Stentor, we further detected several intriguing differences in the enrichment of gene orthologs between the marine Stentor hondawara and the freshwater species, Stentor coeruleus and Stentor pyriformis. The gene groups specifically enriched in Stentor hondawara encode a variety of proteins, including ion channels, pH-responsive proteins, osmoprotectants, amino acid biosynthesis enzymes, and signaling receptors. Additionally, using metagenomics, we detected and isolated, from within our initial genome assembly, the genome of a novel marine bacteria, which we propose is an endosymbiont of Stentor hondawara. This bacterial species is an uncharacterized member of the order Rhodospirillales and appears to be a nutritional factory for the host Stentor hondawara. Taken together, our study provides insight into how Stentor hondawara adapted to a marine environment distinct from the habitats of all the other currently known Stentor species living in freshwater.

evolutionary biology↗

bioRxiv2025

Bypass of Blocking Lesions by RNAPII Impairs the Transcriptional DNA Damage Response

Ultraviolet (UV) irradiation and platinum-based drugs generate bulky DNA lesions that impede transcription elongation by RNA Polymerase II (RNAPII). This transcriptional block triggers a coordinated stress response involving transcription-coupled nucleotide excision repair (TC-NER), removal and degradation of the stalled RNAPII, and global transcriptional shutdown. However, the molecular and cellular consequences of RNAPII bypassing such lesions remain unclear. Here, we identify the acetyltransferase p300 as a key regulator of this transcriptional stress response. p300 interacts with stalled RNAPII and promotes its removal and degradation through a USP7-dependent mechanism. Remarkably, in p300-deficient cells, RNAPII bypasses DNA lesions, allowing transcription to persist despite DNA damage and leading to the production of full-length mRNAs. This sustained transcriptional activity without DNA lesion repair results in increased genome instability and reduced cellular proliferation capacity. These findings reveal the biological consequences of transcribing through transcription-blocking lesions.

molecular biology↗

bioRxiv2022

Contractile ring composition dictates kinetics of in silico contractility

Constriction kinetics of the cytokinetic ring are expected to depend on dynamic adjustment of ring composition, but the impact of component abundance dynamics on ring constriction is understudied. Computational models generally assume that contractile networks maintain constant composition. To test how compositional dynamics affect constriction kinetics, we first measured F-actin, non-muscle myosin II, septin, and anillin during C. elegans zygotic mitosis. A custom microfluidic device that positioned the cell with the division plane parallel to a light sheet allowed even illumination of the cytokinetic ring. Measured component abundances were implemented in an agent-based 3D model of a membrane-associated contractile ring. With constant network composition, constriction occurred with biologically unrealistic kinetics. Measured changes in component quantities elicited realistic constriction kinetics. Simulated networks were more sensitive to changes in motor and filament amounts, than that of crosslinkers and tethers. Our findings highlight the importance of network composition for actomyosin contraction kinetics. SummaryWe created a microfluidic device compatible with high numerical aperture light sheet microscopy to measure cytokinetic ring component abundance in the C. elegans zygote. Implementing measured dynamics into our three-dimensional agent-based model of a contractile ring elicited biologically realistic kinetics.

cell biology↗

bioRxiv2019

Novel cytokinetic ring components limit RhoA activity and contractility

Actomyosin cortical contractility drives many cell shape changes including cytokinetic furrowing. While positive regulation of contractility is well characterized, counterbalancing negative regulation and mechanical brakes are less well understood. The small GTPase RhoA is a central regulator, activating cortical actomyosin contractility during cytokinesis and other events. Here we report how two novel cytokinetic ring components, GCK-1 and CCM-3, participate in a negative feedback loop among RhoA and its cytoskeletal effectors to inhibit contractility. GCK-1 and CCM-3 are recruited by active RhoA and anillin to the cytokinetic ring, where they in turn limit RhoA activity and contractility. This is evidenced by increased RhoA activity, anillin and non-muscle myosin II in the cytokinetic ring, and faster cytokinetic furrowing, following depletion of GCK-1 or CCM-3. GCK-1 or CCM-3 depletion also reduced RGA-3 levels in pulses, and increased baseline RhoA activity and pulsed contractility during zygote polarization. Together, our findings suggest that GCK-1 and CCM-3 regulate cortical actomyosin contractility via negative feedback. SummaryNovel cytokinetic ring proteins, the Ste20 family kinase GCK-1 and its heterodimeric cofactor Cerebral Cavernous Malformations-3, close a negative feedback loop involving the RhoA GAP RGA-3/4, RhoA, and its cytoskeletal effector anillin to limit actomyosin contractility in cytokinesis and during polarization of the C. elegans zygote.

cell biology↗

bioRxiv2017

Crosslinkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis

Cytokinesis and other cell shape changes are driven by the actomyosin contractile cytoskeleton. The molecular rearrangements that bring about contractility in non-muscle cells are currently debated. Specifically, both filament sliding by myosin motors, as well as cytoskeletal crosslinking by myosins and non-motor crosslinkers, are thought to promote contractility. Here, we examined how the abundance of motor and non-motor crosslinkers controls the speed of cytokinetic furrowing. We built a minimal model to simulate the contractile dynamics of the C. elegans zygote cytokinetic ring. This model predicted that intermediate levels of non-motor crosslinkers would allow maximal contraction speed, which we found to be the case for the scaffold protein anillin, in vivo. Our model also demonstrated a non-linear relationship between the abundance of motor ensembles and contraction speed. In vivo, thorough depletion of non-muscle myosin II delayed furrow initiation, slowed F-actin alignment, and reduced maximum contraction speed, but partial depletion allowed faster-than-expected kinetics. Thus, both motor and non-motor crosslinkers promote cytokinetic ring closure when present at low levels, but act as a brake when present at higher levels. Together, our findings extend the growing appreciation for the roles of crosslinkers, but reveal that they not only drive but also brake cytoskeletal remodeling.

cell biology↗