Biology subjects

Hsueh, Y.-P.

Publications and source records attributed to Hsueh, Y.-P..

At least 19 recordsLinked to original sources

bioRxiv2026

Nutrient and prey-sensing signaling pathways converge on the sphingolipid methyltransferase SMT1 to regulate trap formation in a predatory fungus

The nematode trapping fungus Arthrobotrys oligospora transitions from saprophytic growth to a predatory lifestyle by forming adhesive traps in response to nutrient limitation and nematode derived cues. How nutrient availability integrates with prey sensing to control trap formation remains unclear. The presence of glucose can suppress trap formation and we found that Cre1, a conserved transcription factor that regulates the carbon catabolite repression pathway in fungi is essential for trap formation. Comparative transcriptomics and functional studies identified SMT1, which encodes a sphingolipid C9 methyltransferase, as a Cre1-dependent target that is sufficient to restore trap formation defect in the cre1 mutant. Smt1 contributes to the formation of sterol-enriched membrane domain at the tip of a growing trap hyphae and thus affects trap morphogenesis. We further discovered that the expression of SMT1 depends on both Cre1 and another transcription factor Ste12 that acts downstream of the pheromone response MAPK pathway critical for prey-sensing. These findings reveal functional crosstalk between Cre1 and Ste12 where both transcription factors are required for the expression of SMT1 and demonstrate that a predatory fungus integrates nutrient and prey-derived signals to regulate predatory lifestyle switching.

microbiology↗

bioRxiv2026

A nematode-trapping fungus orchestrates polarity cues, septins, and NOX signaling for trap formation

The ability to reprogram cell morphogenesis in response to environmental cues is fundamental to microbial adaptation and survival. The nematode-trapping fungus Arthrobotrys oligospora exemplifies this plasticity by developing adhesive traps to capture nematodes. This morphological transition involves spatial reorientation of cell polarity, cytoskeletal remodeling, and cell fusion. However, the molecular mechanisms that coordinate these processes remain unclear. Using live-cell imaging, genetics, and functional assays, we demonstrated that cell polarity proteins localize to hyphal tips to direct growth, while actin and septins assemble at the curving inner rim to shape trap architecture. Conserved NADPH oxidases are induced by the presence of nematodes and are required for the recruitment of cell polarity proteins and cytoskeletal factors to promote trap cell fusion. Together, these findings reveal that polarity cues, cytoskeletal organization, and reactive oxygen species signaling are integrated to orchestrate nematode-induced trap development, establishing nematode-trapping fungi as a versatile model to study fungal cell biology.

cell biology↗

bioRxiv2026

Ammonium Transporters Govern Nutrient Sensing and Trap Induction in the Nematode-Trapping Fungi Arthrobotrys oligospora

To survive nutrient scarcity, organisms must detect environmental cues and acquire essential resources efficiently. Under nutrient-limiting conditions, nematode-trapping fungi (NTF) such as Arthrobotrys oligospora form specialized traps to capture nematodes; this transition can be suppressed by the ready availability of carbon and nitrogen. Ammonium transporters of the MEP family are key regulators of nitrogen sensing and uptake across all forms of life. We identified three MEP genes in A. oligospora based on protein sequence homology. Functional assays revealed that loss of the MEP genes alters the funguss ability to produce traps, without affecting the morphology of the traps or their ability to function in catching nematodes. Heterologous expression in Saccharomyces cerevisiae revealed functional conservation of Mep transporter subclasses. Together, the Mep transporters of A. oligospora contribute to ammonium-regulated trap induction.

genetics↗

bioRxiv2025

Establishment of a Congenic Strain for the Oyster mushroom reveals the Structure and Evolution of Mating-Type Loci

Pleurotus ostreatus, a widely cultivated edible oyster mushroom, is an ecologically versatile species with applications in biotechnology, agriculture, and food production. It functions as a decomposer and in nutrient-limited conditions it enhances its survival by using a potent toxin to prey on nematodes. Its adaptability is further regulated by sexual reproduction, which follows a tetrapolar mating system governed by two unlinked, multiallelic loci, matA and matB. The two mating-compatible monokaryotic strains PC9 and PC15, derived from the parental dikaryon strain N001, exhibit significant physiological differences. PC9 grows robustly in laboratory conditions, whereas PC15 grows more slowly, making PC9 the preferred strain for research. To advance P. ostreatus as a genetic model, we characterized the mating-type (MAT) loci of both monokaryon strains and developed a congenic strain. We analyzed the MAT loci in multiple P. ostreatus strains, and identified 11 A and 12 B alleles among twelve haplotypes, confirming their multiallelic nature. Using genetic backcrosses, we introgressed the matA and matB loci from PC15 into the PC9 genetic background to generate the congenic strain PC9.15. After sequencing and assembling a high-quality and contiguous genome for PC9.15, we confirmed that the genomes of PC9.15 and PC9 are 99% similar, with the only major difference placed at the matA and matB loci. Author SummaryMushrooms are not just decomposers-they can also be predators. The oyster mushroom Pleurotus ostreatus is an ecologically adaptable species that thrives by breaking down plant material and preying on nematodes using a potent toxin that triggers rapid paralysis of nematode prey. In addition to its ability to switch from saprophyte to predator, another feature contributing to the ecological success of Pleurotus is its reproductive strategy. P. ostreatus reproduces sexually through a tetrapolar mating-type system, governed by two unlinked mating loci, matA and matB. These loci determine mating compatibility and contribute to genetic diversity, yet their precise structure and allelic diversity remain unclear. In this study, we characterized the matA and matB loci in P. ostreatus strains PC9 and PC15 and analyzed MAT loci across multiple strains, confirming their multiallelic nature. To enhance P. ostreatus as a genetic model, we developed the congenic strain PC9.15 by introgressing MAT alleles from PC15 into the PC9 genetic background through genetic backcrosses. Genome sequencing confirmed that PC9.15 closely matches the genome of PC9, except at the MAT loci. This study expands our understanding of mating-type diversity in P. ostreatus, introduces PC9.15 as a valuable tool for genetic studies and controlled crosses, and facilitates the development of P. ostreatus as a model system for fungal biology.

genetics↗

bioRxiv2025

Abnormal synaptic proteomes, impaired neural ensembles, and defective behaviors in autism mouse models are ameliorated by dietary intervention with nutrient mixtures

Autism spectrum disorders (ASD) are a group of heterogeneous, behaviorally defined neurodevelopmental conditions influenced by both genetic and environmental factors. Here, we show that nutrients--an important environmental factor--can modulate synaptic proteomes, reconfigure neural ensembles, and improve social behaviors in ASD mouse genetic models. We analyzed Tbr1+/- mice, a well-established model of ASD, using proteomic approaches and in vivo calcium imaging. Synaptic and metabolic proteomes were found to be sensitive to Tbr1 haploinsufficiency. Our results also revealed that Tbr1 haploinsufficiency promotes hyperactivation and hyperconnectivity of basolateral amygdala (BLA) neurons, enhancing the activity correlation between individual neurons and their corresponding ensembles. Zinc, branched-chain amino acids (BCAA), and serine--all nutrients known to regulate synapse formation and activity--were then combined into supplement cocktails and administered to Tbr1+/- mice. This treatment altered synaptic and metabolic proteomes and normalized the activity and connectivity of the BLA in Tbr1+/- mice during social interactions. We further show that although a low dose of individual nutrients did not alter social behaviors, treatment with supplement cocktails containing low-dose individual nutrients improved social behaviors and associative memory of Tbr1+/- mice, implying a synergistic effect of combining low-dose zinc, BCAA, and serine. Moreover, the supplement cocktails also improved social behaviors in Nf1+/- and Cttnbp2+/M120I mice, two additional ASD mouse models. Thus, our findings reveal aberrant neural connectivity in the BLA of Tbr1+/- mice and indicate that dietary supplementation with zinc, BCAA, and/or serine offers a safe and accessible approach to mitigate neural connectivity and social behaviors across multiple ASD models.

neuroscience↗

bioRxiv2025

Cuticular collagens mediate cross-kingdom predator-prey interactions between nematodes and trapping fungi

Adhesive interactions, mediated by specific molecular and structural mechanisms, are fundamental to host-pathogen and predator-prey relationships, driving evolutionary dynamics and ecological interactions. Here, we investigate the cellular and molecular basis of adhesion between the nematode Caenorhabditis elegans and its natural predator the nematode-trapping fungus Arthrobotrys oligospora, which employs specialized adhesive nets to capture its prey. Using forward genetic screens, we identified C. elegans mutants that escape fungal traps and revealed the nuclear hormone receptor NHR-66 as a key regulator of fungal-nematode adhesion. Loss-of-function mutations in nhr-66 conferred resistance to fungal trapping through the downregulation of a large subset of cuticular collagen genes. Restoring collagen gene expression in nhr-66 mutants abolished the escape phenotype, highlighting the essential role of these structural proteins in fungal-nematode adhesion. Furthermore, sequence analysis of natural C. elegans populations revealed no obvious loss-of-function variants in nhr-66, suggesting selective pressures exist that balance adhesion-mediated predation risk with physiological robustness. We observed that loss of nhr-66 function resulted in a trade-off of increased hypersensitivity to hypoosmotic stress and cuticular fragility. These findings underscore the pivotal role of structural proteins in shaping ecological interactions and the evolutionary arms race between predator and prey.

evolutionary biology↗

bioRxiv2025

Assigning Targetable Molecular Pathways to Transdiagnostic Subgroups Across Autism and Related Neurodevelopmental Disorders

The heterogeneity of autism and related neurodevelopmental conditions has impeded accurate prognoses and treatment discovery. Using translational neuroimaging across 135 mouse models (3,515 mice) and two human MRI datasets (n = 1,234 and n = 1,015), we derived participant subgroups from shared neuroanatomical features. These subgroups did not distinguish autism, ADHD, or OCD diagnoses and only modestly differentiated cognitive and behavioural phenotypes. Instead, they mapped onto four molecular pathways: (1) synaptic function; (2) MAPK and Wnt signalling; (3) chromatin modification and cellular stress responses; and (4) broader chromatin, immune, and second-messenger signalling pathways. This framework bridges preclinical models and idiopathic human neurodevelopmental conditions, linking patients to biologically relevant molecular mechanisms.

neuroscience↗

bioRxiv2025

Mismatch repair and homologous recombination are yin-yang partners in hybrid zygote meiosis

Rad51 and meiosis-specific Dmc1 catalyze homologous recombination (HR) between maternal and paternal chromosomes during meiosis in many sexual eukaryotes, generating three interhomolog (IH) recombination products: noncrossovers (NCOs), class I crossovers (COs), and class II COs. Some COs form chiasmata, which physically connect homologous chromosomes and ensure proper chromosome segregation during meiosis I. Meiosis is highly relevant to speciation, with the mismatch repair (MMR) system believed to prevent IH-HR, leading to postzygotic isolation between closely related species. We report that several Saccharomyces cerevisiae HR proteins exhibit anti-MMR activities, including Rad51, Rad54, and synapsis-promoting ZMM proteins (Mer3, Zip1, Zip4, and Msh4) in SK1/S288c hybrid zygotes. Srs2 (an ortholog of Escherichia coli helicase UvrD) facilitates MMR by dissembling Rad51-ssDNA presynaptic filaments. Rad51 antagonizes MMR and Srs2 to catalyze D-loop formation. Rad54s anti-MMR activity acts after Srs2 and outcompetes its pro-HR function to promote Rad51-mediated IH-HR in hybrid zygotes. Dmc1 does not possess anti-MMR activity, but exhibits better mismatch tolerability than Rad51. Following D-loop formation mediated by Dmc1 and/or Rad51, ZMM proteins promote class I IH-CO formation while limiting MMR to promote NCO formation by Sgs1 (an ortholog of E. coli RecQ helicase) and prevent class II IH-CO formation by the Mms4*Mus81 endonuclease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/636946v2_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@db6794org.highwire.dtl.DTLVardef@6d5947org.highwire.dtl.DTLVardef@1004489org.highwire.dtl.DTLVardef@938403_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMMR and HR antagonize each other in intraspecies hybrid zygotes. C_LIO_LIThe HR proteins Rad51, Rad54, and ZMM exhibit anti-MMR activities. C_LIO_LIMMR overrides HR in hybrid zygotes with anti-MMR mutations, causing hybrid sterility. C_LI

genetics↗

bioRxiv2025

Sex-biased zinc responses modulate ribosome biogenesis, protein synthesis and social defects in Cttnbp2 mutant mice

Autism spectrum disorders (ASD) are neurodevelopmental conditions influenced by genetic mutations, dietary factors, and sex-specific mechanisms, yet the interplay of these factors remains elusive. Here, we investigate the sex-biased responses of mutant mice carrying an ASD-associated mutation in Cttnbp2 to dietary zinc supplementation using behavioral assays, proteomic and bioinformatic analyses, and puromycin pulse labeling to assess protein synthesis. Our results demonstrate that zinc supplementation enhances ribosome biogenesis and increases the density and size of dendritic spines in male Cttnbp2 mutant mice, alleviating male-biased social deficits. Analyses of neuronal cultures further revealed that neurons, not astrocytes, respond to zinc to enhance protein synthesis. In contrast, female Cttnbp2 mutants exhibit resilience to differential zinc intake, even under zinc deprivation. Elevated mTOR phosphorylation and increased protein levels of translational initiation factors in female brains may provide a protective mechanism, reducing their sensitivity to zinc deficiency. Cttnbp2 mutations heighten male vulnerability to zinc deprivation, impairing social behaviors. These findings highlight zinc-regulated ribosome biogenesis and protein synthesis as critical mediators of sex-specific ASD phenotypes, offering new insights into dietary interventions.

neuroscience↗

bioRxiv2025

Shared Alteration of Whole-Brain Connectivity and Olfactory Deficits in Multiple Autism Mouse Models

Autism spectrum disorder (ASD) is a disconnection condition influenced by both heterogeneous genetic and environmental factors, yet it remains unclear whether common connectivity deficits exist. Here, we demonstrate that different ASD-linked mutations lead to distinct circuit abnormalities but share deficits in the piriform cortex and olfactory discrimination. Using advanced artificial intelligence, we developed a whole-brain mapping platform to analyze the distribution of the Thy1-YFP projection neurons in three ASD mouse models (Tbr1+/-, Nf1+/-, Vcp+/R95G). Our analysis revealed changes in axonal patterns and neuronal distribution, indicating deficits in projection neuron differentiation and maintenance. Notably, the piriform cortex consistently exhibited reduced YFP+ cells and signals and impaired functionality across all models. Visual and somatosensory cortices were also affected, but the patterns varied. These findings highlight that the sensory regions, especially the piriform cortex, are susceptible to ASD-related mutations, strengthening the notion that different sensory experiences are common in ASD. HighlightsO_LIAI-powered whole-mouse brain quantification accelerates neural connectivity study. C_LIO_LIAutism-linked mutations lead to various circuit abnormalities of Thy1-YFP neurons. C_LIO_LIMultiple sensory regions all exhibit circuit deficits among the three autism models. C_LIO_LIAbnormalities of olfaction and piriform cortex circuits are common in autism models. C_LI

neuroscience↗

bioRxiv2024

Ki67 regulates nuclear lipid accumulation at the chromosomal periphery to facilitate chromosome individualization during mitosis

Nuclear lipids play roles in regulatory processes such as signaling, transcriptional regulation, and DNA repair. In this report, we demonstrate that nuclear lipids may contribute to Ki-67-regulated chromosome integrity during mitosis. In COS-7 cells, nuclear lipids are enriched at the perichromosomal layer and excluded from intrachromosomal regions during early mitosis, but are then detected in intrachromosomal regions during late mitosis, as revealed by TT-ExM, an improved expansion microscopy technique that enables high-sensitivity, super-resolution imaging of proteins, lipids, and nuclear DNA. The nuclear non-histone protein Ki-67 acts as a surfactant to form a repulsive molecular brush around fully condensed sister chromatids in early mitosis, preventing the diffusion or penetration of nuclear lipids into intrachromosomal regions. Ki-67 is phosphorylated during mitosis by cyclin-dependent kinase 1 (CDK1), the best-known master regulator of the cell cycle. Both Ki-67 knockdown and reduced Ki-67 phosphorylation by CDK1 inhibitors allow nuclear lipids to penetrate chromosomal regions. Thus, both Ki-67 protein level and phosphorylation status during mitosis appear to influence the perichromosomal distribution of nuclear lipids. Ki-67 knockdown and CDK1 inhibition also lead to uneven chromosome disjunction between daughter cells, highlighting the critical role of this regulatory mechanism in ensuring accurate chromosome segregation. Given that Ki-67 has been proposed to promote chromosome individualization during open mitosis in vertebrates, our results reveal that nuclear lipid enrichment at the perichromosomal layer enhances Ki-67s ability to form a protective chromosomal envelope, which is critical for correct chromosome segregation and maintenance of genome integrity during mitosis.

cell biology↗

bioRxiv2024

Predation by nematode-trapping fungus triggers mechanosensory-dependent quiescence in C. elegans

Predation can induce behavioral changes in prey, yet the molecular and neuronal mechanisms underlying prey responses remain poorly understood. Here, we investigated how the nematode Caenorhabditis elegans responds to predation by the nematode-trapping fungus, Arthrobotrys oligospora. We found that A. oligospora predation induced quiescence in C. elegans showing rapid cessation of pharyngeal pumping and movement. Calcium imaging revealed that this quiescence was regulated by the activation of sleep-promoting neurons, ALA and RIS. Genetic analyses demonstrated that ALA were essential for pharyngeal pumping inhibition, whereas both ALA and RIS contributed to movement cessation. Transcriptomic analysis in C. elegans showed the upregulation of immune defense genes in response to A. oligospora predation. We demonstrated that mechanosensation was required for pumping inhibition and transcriptomic regulation upon A. oligospora trapping. These findings suggest that physical constraints imposed by fungal traps trigger a stress-induced quiescence and the upregulation of defense genes in C. elegans. We suggest that trapping-induced quiescence might be a predation strategy used by sessile predators to prevail in the evolutionary arms race.

microbiology↗

bioRxiv2023

Tbr1 autism mouse model displays altered structural and functional amygdalar connectivity and abnormal whole-brain synchronization

Autism spectrum disorders (ASD) are considered neural dysconnectivity syndromes. To better understand ASD and uncover potential treatments, it is imperative to know and dissect the connectivity deficits under conditions of autism. Here, we apply a whole-brain immunostaining and quantification platform to demonstrate impaired structural and functional connectivity and aberrant whole-brain synchronization in a Tbr1+/- autism mouse model. We express a channelrhodopsin variant oChIEF fused with Citrine at the basolateral amygdala (BLA) to outline the axonal projections of BLA neurons. By activating the BLA under blue light theta-burst stimulation (TBS), we then evaluate the effect of BLA activation on C-FOS expression at a whole brain level to represent neural activity. We show that Tbr1 haploinsufficiency almost completely disrupts contralateral BLA axonal projections and results in mistargeting in both ipsilateral and contralateral hemispheres, thereby globally altering BLA functional connectivity. Based on correlated C-FOS expression among brain regions, we further show that Tbr1 deficiency severely disrupts whole-brain synchronization in the absence of salient stimulation. Tbr1+/- and wild-type (WT) mice exhibit opposing responses to TBS-induced amygdalar activation, reducing synchronization in WT mice but enhancing it in Tbr1+/- mice. Whole-brain modular organization and inter-module connectivity are also affected by Tbr1 deficiency and amygdalar activation. Following BLA activation by TBS, the synchronizations of the whole brain and the default mode network, a specific subnetwork highly relevant to ASD, are enhanced in Tbr1+/- mice, implying a potential ameliorating effect of amygdalar stimulation on brain function. Indeed, TBS-mediated BLA activation increases nose-to-nose social interactions of Tbr1+/- mice, strengthening evidence for the role of amygdalar connectivity in social behaviors. Our high-resolution analytical platform reveals the inter- and intra-hemispheric connectopathies arising from ASD. Our study emphasizes the defective synchronization at a whole-brain scale caused by Tbr1 deficiency and implies a potential beneficial effect of deep brain stimulation at the amygdala for TBR1-linked autism.

neuroscience↗

bioRxiv2022

SARM1 detection in oligodendrocytes but not Schwann cells though sarm1/Sarm1 deletion does not perturb CNS nor PNS myelination in zebrafish and mice.

SARM1 is a central regulator of programmed axon death and is required to initiate axon self-destruction after traumatic and toxic insults to the nervous system. Abnormal activation of this axon degeneration pathway is increasingly recognized as a contributor to human neurological disease and SARM1 knockdown or inhibition has become an attractive therapeutic strategy to preserve axon loss in a variety of disorders of the peripheral and central nervous system. Despite this, it remains unknown whether Sarm1/SARM1 is present in myelinating glia and whether it plays a role in myelination in the PNS or CNS. It is important to answer these questions to understand whether future therapies inhibiting SARM1 function may have unintended deleterious impacts on myelination. Here we show that Sarm1 mRNA is present in oligodendrocytes in zebrafish but only detectable at low levels in Schwann cells in both zebrafish and mice. We find SARM1 protein is readily detectable in murine oligodendrocytes in vitro and in vivo and activation of endogenous SARM1 in oligodendrocytes induces cell death. In contrast, SARM1 protein is not detectable in Schwann cells and satellite glia in the adult murine nervous system. Cultured Schwann cells contain negligible functional SARM1 and are insensitive to specific SARM1 activators. Using zebrafish and mouse Sarm1 mutants, we show that SARM1 is not required for initiation of myelination nor myelin sheath maintenance by oligodendrocytes and Schwann cells. Thus, strategies to inhibit SARM1 function in the nervous system to treat neurological disease are unlikely to perturb myelination in humans. Main PointsO_LISARM1 protein is detectable in oligodendrocytes but not in Schwann cells C_LIO_LIOligodendrocytes but not Schwann cells die in response to endogenous SARM1 activation C_LIO_LICNS nor PNS myelination, in zebrafish and mice, is hindered by loss of sarm1/Sarm1 C_LI

neuroscience↗

bioRxiv2021

Sex-biased response to and brain cell infection by SARS-CoV-2 in a highly susceptible human ACE2 transgenic model

The COVID-19 pandemic is caused by SARS-CoV-2 infection. Human angiotensin-converting enzyme II (hACE2) has been identified as the receptor enabling SARS-CoV-2 host entry. To establish a mouse model for COVID-19, we generated transgenic mouse lines using the (HS4)2-pCAG-hACE2-HA-(HS4)2 transgene cassette, which expresses HA-tagged hACE2 under control of the CAG promoter and is flanked by HS4 insulators. Expression levels of the hACE2 transgene are respectively higher in lung, brain and kidney of our CAG-hACE2 transgenic mice and relatively lower in duodenum, heart and liver. The CAG-hACE2 mice are highly susceptibility to SARS-CoV-2 infection, with 100 PFU of SARS-CoV-2 being sufficient to induce 87.5% mortality at 9 days post-infection and resulting in a sole (female) survivor. Mortality was 100% at the higher titer of 1000 PFU. At lower viral titers, we also found that female mice exposed to SARS-CoV-2 infection suffered much less weight loss than male mice, implying sex-biased responses to SARS-CoV-2 infection. We subjected neuronal cultures to SARS-CoV-2 pseudovirus infection to ascertain the susceptibilities of neurons and astrocytes. Moreover, we observed that expression of SARS-CoV-2 Spike protein alters the synaptic responses of cultured neurons. Our transgenic mice may serve as a model for severe COVID-19 and sex-biased responses to SARS-CoV-2 infection, aiding in the development of vaccines and therapeutic treatments for this disease.

microbiology↗

bioRxiv2020

Intrinsic disorder codes for leaps of protein expression

Serine(S)/threonine(T)-glutamine(Q) cluster domains (SCDs), polyglutamine (polyQ) tracts and polyglutamine/asparagine (polyQ/N) tracts are Q-rich motifs found in many proteins. SCDs often are intrinsically disordered regions that mediate protein phosphorylation and protein-protein interactions. PolyQ and polyQ/N tracts are structurally flexible sequences that trigger protein aggregation. We report that due to their high percentages of STQ or STQN amino acid content, four SCDs and three prion-causing Q/N-rich motifs of yeast proteins possess autonomous protein expression-enhancing activities. Since these Q-rich motifs can endow proteins with structural and functional plasticity, we suggest that they represent useful toolkits for evolutionary novelty. Comparative Gene Ontology (GO) analyses of the near-complete proteomes of 27 representative model eukaryotes reveal that Q-rich motifs prevail in proteins involved in specialized biological processes, including Saccharomyces cerevisiae RNA-mediated transposition and pseudohyphal growth, Candida albicans filamentous growth, ciliate peptidyl-glutamic acid modification and microtubule-based movement, Tetrahymena thermophila xylan catabolism and meiosis, Dictyostelium discoideum development and sexual cycles, Plasmodium falciparum infection, and the nervous systems of Drosophila melanogaster, Mus musculus and Homo sapiens. We also show that Q-rich-motif proteins are expanded massively in ten ciliates with reassigned TAAQ and TAGQ codons. Notably, the usage frequency of CAGQ is much lower in ciliates with reassigned TAAQ and TAGQ codons than in organisms with expanded and unstable Q runs (e.g., D. melanogaster and H. sapiens), indicating that the use of noncanonical stop codons in ciliates may have coevolved with codon usage biases to avoid triplet repeat disorders mediated by CAG/GTC replication slippage.

biochemistry↗

bioRxiv2020

SARS-CoV-2 D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) exhibits two major variants based on mutations of its spike protein, i.e., the D614 prototype and G614 variant. Although neurological symptoms have been frequently reported in patients, it is still unclear whether SARS-CoV-2 impairs neuronal activity or function. Here, we show that expression of both D614 and G614 spike proteins is sufficient to induce phenotypes of impaired neuronal morphology, including defective dendritic spines and shortened dendritic length. Using spike protein-specific monoclonal antibodies, we found that D614 and G614 spike proteins show differential S1/S2 cleavage and cell fusion efficiency. Our findings provide an explanation for higher transmission of the G614 variant and the neurological manifestations observed in COVID-19 patients.

neuroscience↗

bioRxiv2020

Forward genetic screens identified mutants with defects in trap morphogenesis in the nematode-trapping fungus Arthrobotrys oligospora

Nematode-trapping fungi (NTF) are carnivorous fungi that prey on nematodes under nutrient-poor conditions via specialized hyphae that function as traps. The molecular mechanisms involved in the interactions between nematode-trapping fungi and their nematode prey are largely unknown. In this study, we conducted forward genetic screens to identify potential genes and pathways that are involved in trap morphogenesis and predation in the NTF Arthrobotrys oligospora. Using Ethyl methanesulfonate and UV as the mutagens, we generated 5552 randomly-mutagenized A. oligospora strains and identified 15 mutants with strong defects in trap morphogenesis. Whole genome sequencing and bioinformatic analyses revealed mutations in genes with roles in signaling, transcription or membrane transport that may contribute to the defects of trap morphogenesis in these mutants. We further conducted functional analyses on a candidate gene, YBP-1, and demonstrate that mutation of that gene was causative of the phenotypes observed in one of the mutants. The methods established in this study might provide helpful insights for establishing forward genetic screening methods for other non-model fungal species.

molecular biology↗