Biology subjects

Ono, K.

Publications and source records attributed to Ono, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Autopsy-based longitudinal multi-organ high-dimensional profiling reveals lineage plasticity in TRK-inhibitor-resistant secretory breast carcinoma

Secretory breast carcinoma (SBC) is typically indolent, yet mechanisms underlying aggressiveness and therapeutic resistance to tropomyosin receptor kinase inhibitors (TRKi) remain unclear. Autopsy-based longitudinal multi-organ high-dimensional profiling of metastatic TRKi-resistant SBC demonstrated histopathological heterogeneity, including secretory and squamous components, arising from a shared clonal origin. Integrated genomic and transcriptomic analyses revealed hierarchical transcriptional rewiring consistent with a lineage-plastic state, suggesting a potential link to tumor aggressiveness and therapeutic resistance.

pathology↗

bioRxiv2026

The Nkx2.3-Nr5a1 gene cascade plays a crucial role in spleen-specific vascular architecture and marginal zone formation

NR5A1 is a nuclear receptor and master regulator of steroidogenic tissue development and steroid hormone biosynthesis in the adrenal glands and gonads. Although NR5A1 is expressed in splenic vascular endothelial cells, its function in the adult spleen remains unclear. Using single-cell transcriptomics in mice, we show that NR5A1-positive endothelial cells are heterogeneous and exhibit distinct phenotypes according to their localization in the splenic sinus or marginal sinus. To assess NR5A1 function, we generated a spleen-specific Nr5a1 enhancer deletion model. Enhancer loss resulted in reduced spleen size and ablation of the marginal zone and marginal sinus. In addition, 21-hydroxylase activity in splenic sinusoidal endothelial cells was reduced, particularly in females, leading to decreased levels of adrenocortical steroids in the spleen. Enhancer deletion also induced ectopic lymphatic-like and high endothelial venule-like vasculature similar to those observed in Nkx2.3-deficient mice. Consistently, mutation of the NKX2.3-binding motif within the enhancer abolished NR5A1 expression. Together, these findings identify an Nkx2.3[->]Nr5a1 regulatory axis essential for spleen-specific endothelial cell differentiation and splenic architecture required for blood filtration and marginal zone formation.

developmental biology↗

bioRxiv2026

The REFLEX system enables in vivo identification of perivascular angiogenic macrophages in the heart

Direct identification of physically interacting cells in vivo remains challenging because conventional interactome analyses infer signaling partners from transcriptomes and cannot reveal which cells are in direct contact. In pressure-overload induced cardiac remodeling, VEGF-A plays a central role in the maintenance of vascular integrity and cardiac function. However, the cell type which produces VEGF-A and how the VEGF-A peptide is delivered to vascular endothelial cells remains unclear. Here, we developed a genetically encoded platform that combines REFLEX mice with HUNTERuni-seq, enabling unbiased detection and transcriptional profiling of the cells that physically interact with vascular endothelial cells. The REFLEX and HUNTERuni-seq approach identified subpopulations of Vegfa positive macrophages which we named perivascular angiogenic macrophages (PVAMs). Although the amount of VEGF-A in PVAMs is small, loss of VEGF-A in PVAMs impaired angiogenesis and systolic function during pressure overload. We additionally show that direct contact between PVAMs and endothelial cells is critical for the delivery of VEGF-A to endothelial cells. Conventional interactome analysis predicted that cardiomyocytes as dominant sources of VEGF-A in the heart. However, cardiomyocyte Vegfa deletion had no effect on capillary density nor systolic function in a model of heart failure. These results suggest that VEGF-A signaling does not rely on free diffusion through the interstitium and that cellular proximity and physical contact between PVAMs and endothelial cells are the key determinants of effective signal delivery. Together, these findings establish REFLEX and HUNTERuni-seq as a versatile platform for uncovering biologically critical cell-to-cell interactions and provide new insight into intercellular communication in pathological tissue contexts.

cell biology↗

bioRxiv2025

Linear Z-line-like alignment of capping protein in obliquely striated muscle of the nematode C. elegans suggests that dense bodies are not equivalent to Z-lines

Many invertebrates have obliquely striated muscles, in which neighboring thin and thick filaments are staggered and aligned in an oblique manner. This type of muscle allows force production over a wide range of lengths and is beneficial for soft-bodied animals. Unlike cross-striated muscles of vertebrates, most of obliquely striated muscles lack distinct Z-lines and, instead, have dense bodies. Because the dense bodies are located in the middle of the I-bands and contain -actinin, the dogma is that dense bodies are equivalent to the Z-lines anchoring the actin barbed ends. However, we present evidence that the barbed ends of sarcomeric actin filaments in the nematode Caenorhabditis elegans body wall muscle are aligned in a linear Z-line-like arrangement without converging at the dense bodies. Colocalization of F-actin and ATN-1/-actinin was minimal. Furthermore, CAP-1, an -subunit of capping protein/CapZ, was linearly aligned in the middle of the I-bands without concentration at the dense bodies. This linear CAP-1 alignment was maintained in the absence of ATN-1. These results demonstrate that the actin barbed ends are not directly anchored to the dense bodies. Depletion of the capping protein subunit, CAP-1 or CAP-2, caused embryonic or larval lethality with severe actin disorganization in the body wall muscle, indicating that barbed-end regulation by capping protein is essential for sarcomere assembly. These results contradict the current view of the sarcomere organization in C. elegans muscle and suggest a new model of a linear Z-line-like arrangement of actin barbed ends. Significance StatementO_LIWithout clear evidence, there has been a notion that actin filaments are directly anchored to the dense bodies in C. elegans striated muscle. C_LIO_LICapping protein localizes in a linear Z-line-like alignment in C. elegans muscle without concentrating at the dense bodies, indicating that the actin barbed ends are not directly anchored at the dense bodies. C_LIO_LIDepletion of capping protein causes severe sarcomere defects in embryos and larvae indicating a critical role of capping protein in sarcomere assembly. C_LI

cell biology↗

bioRxiv2025

Proteomic and in silico dissection of MetaAggregates in amyotrophic lateral sclerosis brains

RNA-binding proteins (RBPs), key translation regulators, are thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The pathological entities associated with ALS are known as "MetaAggregates": heterogeneous coaggregates composed of amyloids, RBPs, and RNA G-quadruplexes (rG4s). In this study, to explore the molecular constituents of ALS-associated MetaAggregates, we developed a proteomic approach using a psoralen-conjugated RBP and crosslinked it with a biotinylated rG4 to enable the isolation of MetaAggregates from ALS brain extracts. Single-cell RNA-seq using in vitro ALS models identified ELAVL4 as a cytoplasmic RBP and revealed the enrichment of an IGFBP2-derived rG4 structure in ALS-specific neurons. Mass spectrometry and amyloidogenicity-based principal component analysis revealed 79 candidate proteins with roles in RNA processing, metabolism, trafficking, and stress responses. Docking simulations highlighted a subset of proteins with potential pro-aggregation characteristics, diverse cytosolic associations and functional links to RNA processing relevant to ALS. Through proteomic and in silico dissection of ALS-associated MetaAggregates, the findings of this study establish a conceptual framework for the exploration of unrecognized amyloidogenic drivers of neurodegeneration.

neuroscience↗

bioRxiv2025

Proto-MHC signatures in the lamprey genome

Jawless vertebrates, which diverged from jawed vertebrates approximately 550 million years ago, possess an adaptive immune system characterized by two distinct lineages of lymphocytes bearing unique antigen receptors. However, despite decades of research, the mechanism of antigen presentation in these organisms remains unclear. In this study, we report that chromosomes 22, 50, and 59 in the sea lamprey (Petromyzon marinus) exhibit synteny with the human major histocompatibility complex (MHC) region. The syntenic region spans from DHX16 to RING1 (chromosome 6: 30,517,301-33,034,069) in the human genome (T2T-CHM13v2.0). Similar to the human MHC region, P. marinus chromosome 59 harbors homologs of DDX39B, NOTCH, PBX, TNF, and BRD genes, yet notably lacks the core MHC class I, II, and III (complement) genes. Genotyping of three independent lampreys showed no signatures of balancing selection, a characteristic feature of the human MHC. Additionally, these lamprey chromosomes exhibit synteny with chromosome 9 in amphioxus (Branchiostoma lanceolatum), which contains conserved homologs that form its "proto-MHC." These findings suggest that chromosomes 22, 50, and 59 in P. marinus are a proto-MHC or its paralog.

evolutionary biology↗

bioRxiv2024

Conserved interhemispheric morphogenesis in amniotes preceded the evolution of the corpus callosum

The corpus callosum (CC) is the large axon bundle connecting the telencephalic hemispheres. The CC is formed exclusively in placental mammals, and the lack of comparable structures in other amniotes obscures the evolutionary origin of the CC. We here demonstrate that interhemispheric remodeling, a prior developmental step for CC formation, is highly conserved in non-mammalian amniotes, such as reptiles and birds. In these animal groups, the spatiotemporal dynamics of interhemispheric remodeling are tightly connected with distinct commissural formations. We observed a high degree of similarity between the mammalian CC and reptilian rostral pallial commissure, (RPC) and significant modifications in the avian pallial projection. Furthermore, we determined that Satb2 plays crucial roles in interhemispheric remodeling, which is associated with proper formation of both the CC and RPC in mice and geckoes, via the use of CRISPR-mediated gene-targeting. Our findings suggest that developmental mechanisms for midline remodeling were already present in the common ancestor of amniotes, which contributed to the evolution of eutherian-specific CC formation.

developmental biology↗

bioRxiv2024

Dual expansion routes likely underlie the present-day population structure in a Parnassius butterfly across the Japanese Archipelago

The Japanese Archipelago, comprising a series of isolated yet interconnected islands, had been geographically separated from the Eurasian continent. The linear topography presents a unique biogeographic context for dispersing organisms from the continent. In this study, we utilized mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) variation to elucidate the dispersal history of the Japanese clouded butterfly Parnassius glacialis across the Japanese Archipelago, including North Island (Hokkaido), Main Island (Honshu) and Shikoku Island. Our analysis of mtDNA (COI, COII) at 1192 base pairs (bps) revealed 49 haplotypes and identified three distinct haplotype groups in the network. These groups correspond geographically to East Japan, West Japan, and Chugoku-Shikoku. The Chugoku-Shikoku group is the most ancient lineage. Interestingly, the Chugoku-Shikoku lineage showed a closer network connection to the East Japan lineage than the geographically proximate West Japan lineage. Divergence time estimates suggest that the Chugoku-Shikoku lineage diverged from the continental P. glacialis approximately 3.05 million years ago (MYA). Subsequently, from the Chugoku-Shikoku lineage, the East Japan and West Japan lineages diverged around 1.05 MYA, with the subsequent divergence between the East and West Japan lineages occurring at approximately 0.62 MYA. Based on the 3067 SNP genotypes, population structure analysis revealed five distinct genetic structures within the Japanese Archipelago, indicating geographical differentiation. From the analyses by mtDNA and SNP variations, four primary genetic barriers were identified: between Hokkaido and Honshu, between East and Central Japan, within the Kansai region, and within the Chugoku region. The former three lines corresponded to the Blakiston Line, the Itoigawa-Shizuoka Tectonic Line, and Lake Biwa, respectively. These findings suggest that P. glacialis diverged from the continental P. glacialis and expanded its range across the Japanese Archipelago via the North and South routes, establishing its current distribution.

molecular biology↗

bioRxiv2024

PRDX6 dictates ferroptosis sensitivity by directing cellular selenium mobilization

Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis and prevents unrestrained (phospho)lipid peroxidation by directly reducing phospholipid hydroperoxides (PLOOH) to their corresponding alcohols. However, it remains unclear whether other phospholipid peroxidases can also contribute to ferroptosis prevention, albeit to a varying degree. Here we show that cells lacking GPX4 still exhibit substantial PLOOH reduction capacity, arguing for the presence of alternative PLOOH peroxidases. By scrutinizing potential candidates, we showed that while overexpression of peroxiredoxin 6 (PRDX6), a thiol-specific antioxidant enzyme with reported PLOOH-reducing activity, failed to prevent ferroptosis, its genetic loss markedly sensitizes cancer cells to ferroptosis. Mechanistically, we uncover that PRDX6 facilitates intracellular selenium handling, which is crucial for selenium incorporation into selenoproteins, including GPX4. Consequently, PRDX6 modulates GPX4 expression, thereby dictating the sensitivity of cells to undergo ferroptosis. Our study highlights PRDX6 as a critical factor in ferroptosis prevention by directing cellular selenium mobilization.

cell biology↗

bioRxiv2024

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

BackgroundEndoplasmic reticulum (ER) stress signaling pathways have pivotal roles in atherosclerosis progression. Recently, we have developed Kyoto University Substance (KUS) 121, which selectively inhibits ATPase activities of valosin-containing protein (VCP) and consequently saves intracellular ATP consumption and mitigates ER stress. Methods and ResultsWe assessed the efficacy of KUS121 against atherosclerosis by its daily injection into Apoe-/- mice fed with Western Diet (WD) for 8 weeks. Consequently, KUS121 treatment reduced atherosclerosis progression by approximately 40% in atherosclerotic plaques. Interestingly, we found that C/EBP homologous protein (CHOP), an established ER stress marker, was mainly expressed in plaque endothelium. Therefore, we assessed the action of KUS121 in endothelial cells using the human endothelial cell line (EA.hy926 cells). As a result, KUS121 prevented ER stress-induced apoptosis and downregulated the IRE1 (Inositol-requiring enzyme) -associated inflammatory pathways. Consistent with these in vitro findings, KUS121 treatment also significantly reduced endothelial apoptosis assessed by TUNEL staining and inflammation examined by immunostaining of Nuclear factor kappa B (NF-{kappa}B) and Intercellular adhesion molecule (ICAM) 1 at plaque endothelium. We also demonstrated that KUS121 maintained ATP levels in EA.hy926 cells and atherosclerotic plaque lesions using the single-wavelength or the FRET-based fluorescent ATP sensor. Supplementation of intracellular ATP by Methyl pyruvate (MePyr) attenuated ER stress-induced apoptotic and inflammatory pathways in endothelial cells, which could be the main mechanism how KUS121 reduces ER stress. ConclusionsKUS121 can be a new therapeutic option for atherosclerotic diseases by maintaining intracellular ATP levels and attenuating ER stress-induced apoptosis and inflammation in plaque endothelium.

pathology↗

bioRxiv2024

Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function

Otolith organs in the inner ear and neuromasts in the fish lateral-line harbor two populations of hair cells oriented to detect stimuli in opposing directions. The underlying mechanism is highly conserved: the transcription factor EMX2 is regionally expressed in just one hair cell population and acts through the receptor GPR156 to reverse cell orientation relative to the other population. In mouse and zebrafish, loss of Emx2 results in sensory organs that harbor only one hair cell orientation and are not innervated properly. In zebrafish, Emx2 also confers hair cells with reduced mechanosensory properties. Here, we leverage mouse and zebrafish models lacking GPR156 to determine how detecting stimuli of opposing directions serves vestibular function, and whether GPR156 has other roles besides orienting hair cells. We find that otolith organs in Gpr156 mouse mutants have normal zonal organization and normal type I-II hair cell distribution and mechano-electrical transduction properties. In contrast, gpr156 zebrafish mutants lack the smaller mechanically-evoked signals that characterize Emx2-positive hair cells. Loss of GPR156 does not affect orientation-selectivity of afferents in mouse utricle or zebrafish neuromasts. Consistent with normal otolith organ anatomy and afferent selectivity, Gpr156 mutant mice do not show overt vestibular dysfunction. Instead, performance on two tests that engage otolith organs is significantly altered - swimming and off-vertical-axis rotation. We conclude that GPR156 relays hair cell orientation and transduction information downstream of EMX2, but not selectivity for direction-specific afferents. These results clarify how molecular mechanisms that confer bi-directionality to sensory organs contribute to function, from single hair cell physiology to animal behavior.

neuroscience↗

bioRxiv2023

A Neanderthal/Denisovan GLI3 variant contributes to anatomical variations in mice

Changes in genomic structures underlie phenotypic diversification in organisms. Amino acid-changing mutations affect pleiotropic functions of proteins, although little is known about how mutated proteins are adapted in existing developmental programs. Here we investigate the biological effects of a variant of the GLI3 transcription factor (GLI3R1537C) carried in Neanderthals and Denisovans, which are extinct hominins close to modern humans. R1537C does not compromise protein stability or GLI3 activator-dependent transcriptional activities. In contrast, R1537C affects the regulation of downstream target genes associated with developmental processes. Furthermore, genome-edited mice carrying the Neanderthal/Denisovan GLI3 mutation exhibited various alterations in skeletal morphology. Our data suggest that an extinct hominin-type GLI3 contributes to species-specific anatomical variations, which were tolerated by relaxed constraint in developmental programs during human evolution.

evolutionary biology↗

bioRxiv2022

NDEx IQuery: a multi-method network gene set analysis leveraging the Network Data Exchange

MotivationThe investigation of sets of genes using biological pathways is a common task for researchers and is supported by a wide variety of software tools. This type of analysis generates hypotheses about the biological processes active or modulated in a specific experimental context. ResultsThe NDEx Integrated Query (IQuery) is a new tool for network and pathway-based gene set interpretation that complements or extends existing resources. It combines novel sources of pathways, integration with Cytoscape, and the ability to store and share analysis results. The IQuery web application performs multiple gene set analyses based on diverse pathways and networks stored in NDEx. These include curated pathways from WikiPathways and SIGNOR, published pathway figures from the last 27 years, machine-assembled networks using the INDRA system, and the new NCI-PID v2.0, an updated version of the popular NCI Pathway Interaction Database. IQuerys integration with MSigDB and cBioPortal now provides pathway analysis in the context of these two resources. Availability and ImplementationIQuery is available at https://www.ndexbio.org/iquery and is implemented in Javascript and Java. ContactDexter Pratt (depratt@health.ucsd.edu)

bioinformatics↗

bioRxiv2022

Self-organization, quality control, and preclinical studies of human iPSC-derived retinal sheets for tissue-transplantation therapy

Three-dimensional retinal organoids (3D-retinas) are a promising graft source for transplantation therapy. We previously developed self-organizing culture for 3D-retina generation from human pluripotent stem cells (hPSCs). Here we present a quality control method and preclinical studies for tissue-sheet transplantation. Self-organizing hPSCs differentiated into both retinal and off-target tissues. Gene expression analyses identified the major off-target tissues as eye-related, cortex-like, and spinal cord-like tissues. For quality control, we developed a qPCR-based test in which each hPSC-derived neuroepithelium was dissected into two tissue-sheets: inner-central sheet for transplantation and outer-peripheral sheet for qPCR to ensure retinal tissue selection. During qPCR, tissue-sheets were stored for 3-4 days using a newly developed preservation method. In a rat tumorigenicity study, no transplant-related adverse events were observed. In retinal degeneration model rats, retinal transplants differentiated into mature photoreceptors and exhibited light responses in electrophysiology assays. These results demonstrate our rationale toward self-organizing retinal sheet transplantation therapy.

neuroscience↗

bioRxiv2021

Testing the Tea Bag Index as a potential indicator for assessing litter decomposition in aquatic ecosystems

The Tea Bag Index (TBI) approach is a standardized method for assessing litter decomposition in terrestrial ecosystems. This method allows determination of the stabilized portion of the hydrolysable fraction during the decomposition process, and derivation of a decomposition constant (k) using single measurements of the mass-loss ratios of green and rooibos teas. Although this method is being applied to aquatic systems, it has not been validated in these environments, where initial leaching tends to be higher than in terrestrial ecosystems. Here, we first validated a critical assumption of the TBI method that green tea decomposition plateaus during the standard incubation period of 90 days, and then tested the accuracy of a TBI-based asymptote model using a second model obtained from fitting actual decomposition data. Validation data were obtained by incubating tea bags in water samples taken from a stream, a pond, and the ocean in Kumamoto, Japan. We found that green tea decomposition did not plateau during the 90-day period, contradicting a key assumption of the TBI method. Moreover, the TBI-based asymptote models disagreed with actual decomposition data. Subtracting the leachable fraction from the initial tea mass improved the TBI-based model, but discrepancies with the actual decomposition data remained. Thus, we conclude that the TBI approach, which was developed for a terrestrial environment, is not appropriate for aquatic ecosystems. However, the use of tea bags as a standard material in assessments of aquatic litter decomposition remains beneficial.

ecology↗

bioRxiv2020

A precautionary solution to estimation bias in shaping safe harvest boundaries

Biased estimates of population status are a pervasive conservation problem. This problem has plagued assessments of commercial exploitation of marine species and can threaten the sustainability of both populations and fisheries. We develop a computer-intensive approach to minimize adverse effects of persistent estimation bias in assessments by optimizing operational harvest measures (harvest control rules) with closed-loop simulation of resource-management feedback systems: management strategy evaluation. Using saithe (Pollachius virens), a bottom-water, apex predator in the North Sea, as a real-world case study, we illustrate the approach by first diagnosing robustness of the existing harvest control rule and then optimizing it through propagation of biases (overestimated stock abundance and underestimated fishing pressure) along with select process and observation uncertainties. Analyses showed that severe biases lead to overly optimistic catch limits and then progressively magnify the amplitude of catch fluctuation, thereby posing unacceptably high overharvest risks. Consistent performance of management strategies to conserve the resource can be achieved by developing more robust control rules. These rules explicitly account for estimation bias through a computational grid search for a set of control parameters (threshold abundance that triggers management action, Btrigger, and target exploitation rate, Ftarget) that maximize yield while keeping stock abundance above a precautionary level. When the biases become too severe, optimized control parameters- for saithe, raising Btrigger and lowering Ftarget-would safeguard against overharvest risk (<3.5% probability of stock depletion) and provide short-term stability in catch limit (<20% year-to-year variation), thereby minimizing disruption to fishing communities. The precautionary approach to fine-tuning adaptive risk management through management strategy evaluation offers a powerful tool to better shape sustainable harvest boundaries for exploited resource populations when estimation bias persists. By explicitly accounting for emergent sources of uncertainty our proposed approach ensures effective conservation and sustainable exploitation of living marine resources even under profound uncertainty. Open Research StatementData sets and code utilized for this research are available on Figshare. DOI: https://doi.org/10.6084/m9.figshare.13281266

ecology↗

bioRxiv2020

Are mice born normally with an egg-only diet?

Chicken eggs (egg) contain high amounts of important proteins and fat with a very low amount of carbohydrates, and also contain all vitamins and minerals needed for the chick to develop. We mated 8-week-old mice consuming an egg-only diet, and examined whether mice got pregnant and mice gave birth. Then we continued to raise newborn mice only consuming an egg-only diet compared to normal chew diet. We found that the rate of pregnancy of the mice consuming an egg-only diet was not different from that of the mice consuming normal chew diet. Further, we found that the number of pupus born from the mother consuming only eggs was not different from that of the mother consuming normal chew diet. However, the newborn mice from the mother fed only eggs did not grow healthy when they consume egg-only diet. Only few mice were alive at one month after birth. Then we change the diet just before or just after birth from egg only diet to normal chew diet and we found that both group grew healthy more than one month. These results indicate that mice are born healthy only with egg only diet.

developmental biology↗

bioRxiv2020

Two Caenorhabditis elegans calponin-related proteins have overlapping functions to maintain cytoskeletal integrity and are essential for reproduction

Multicellular organisms have multiple genes encoding calponins and calponin-related proteins, and some of these are known to regulate actin cytoskeletal dynamics and contractility. However, functional similarities and differences among these proteins are largely unknown. In the nematode Caenorhabditis elegans, UNC-87 is a calponin-related protein with seven calponin-like (CLIK) motifs and is required for maintenance of contractile apparatuses in muscle cells. Here, we report that CLIK-1, another calponin-related protein that also contains seven CLIK motifs, has an overlapping function with UNC-87 to maintain actin cytoskeletal integrity in vivo and has both common and different actin-regulatory activities in vitro. CLIK-1 is predominantly expressed in the body wall muscle and somatic gonad, where UNC-87 is also expressed. unc-87 mutation causes cytoskeletal defects in the body wall muscle and somatic gonad, whereas clik-1 depletion alone causes no detectable phenotypes. However, simultaneous depletion of clik-1 and unc-87 caused sterility due to ovulation failure by severely affecting the contractile actin networks in the myoepithelial sheath of the somatic gonad. In vitro, UNC-87 bundles actin filaments. However, CLIK-1 binds to actin filaments without bundling them and is antagonistic to UNC-87 in filament bundling. UNC-87 and CLIK-1 share common functions to inhibit cofilin binding and allow tropomyosin binding to actin filaments, suggesting that both proteins stabilize actin filaments. Thus, partially redundant functions of UNC-87 and CLIK-1 in ovulation is likely mediated by their common actin-regulatory activities, but their distinct activities in actin bundling suggest that they also have different biological functions.

cell biology↗