Biology subjects

Li, W.-C.

Publications and source records attributed to Li, W.-C..

7 recordsLinked to original sources

bioRxiv2026

Gradual evolution of multiplexed spatial coding within a conserved hippocampal scaffold

The hippocampus constructs spatial maps for navigation, yet their format differs markedly across species. Whether divergences reflect ecological adaptation, phylogenetic architecture, or flexible coding strategy within a conserved circuit has been difficult to disentangle. We recorded CA1 in rats and tree shrews (Tupaia belangeri chinensis), a mammal phylogenetically and ecologically between rodents and primates, using identical tasks and analyses. Unlike the position-dominant code of rats, tree shrew CA1 exhibited a hybrid representation: weaker position selectivity, stronger non-positional tuning, and prevalent multiplexing approaching primate characteristics. Multiplexed populations decoded location as accurately as rat position populations while using fewer neurons, suggesting computational advantages of high-dimensional coding. Despite this representational shift, proximo-distal gradient, pattern completion, and global remapping persisted. Representational format can be tuned without altering the underlying circuit. Tree shrews occupy an evolutionary intermediate in which ancestral network dynamics are repurposed for efficient multiplexed coding, tracing a transition toward primate-like spatial representations.

neuroscience↗

bioRxiv2026

Simultaneous whole-cell recording and calcium imaging to reveal electrically coupled neurons in Xenopus tadpoles

Neuronal populations connected by gap junctions can be revealed via dye coupling of small molecules like neurobiotin and lucifer yellow. However, the extent of dye diffusion between neurons varies with connexin subtype, loading method, and neuromodulation. Due to the increasing availability of GCaMP transgenic animals, we explore the possibility of revealing gap junctional coupling using Ca2+ imaging in the Xenopus laevis tadpole motor system. Reliable axo-axonal electrical coupling was previously found in excitatory descending interneurons (dINs) using paired recordings but not with neurobiotin dye coupling. Here, we made whole-cell patch-clamp recordings with Ca2+-supplemented intracellular solution to load Ca2+ into GCaMP6s-expressing neurons, followed by Ca2+ imaging to detect potential Ca2+ diffusion across coupled neurons. Successful membrane breakthroughs led to transient fluorescence increases in the patched neuron. However, increasing the Ca2+ concentration promoted membrane resealing and rapid loss of whole-cell recordings. Regardless of recording duration, loading-triggered fluorescence only lasted up to three minutes, suggesting rapid Ca2+ clearance. Pharmacologically blocking sarcoplasmic /endoplasmic reticulum Ca2+-ATPases and plasma membrane Na+/Ca2+ exchangers did not prolong fluorescence, although sustained fluorescence was achieved with positive current injections. Counter to our expectations, fluorescence increases in Ca2+-loaded dINs did not spread to neighboring dINs. Robust intracellular Ca2+ regulation mechanisms, membrane resealing, and long dIN axons likely hindered intercellular Ca2+ diffusion. Therefore, this approach is not appropriate for revealing electrical coupling within this system.

neuroscience↗

bioRxiv2023

A PARP14/TARG1-Regulated RACK1 MARylation Cycle Drives Stress Granule Dynamics in Ovarian Cancer Cells

Mono(ADP-ribosyl)ation (MARylation) is emerging as a critical regulator of ribosome function and translation. Herein, we demonstrate that RACK1, an integral component of the ribosome, is MARylated on three acidic residues by the mono(ADP-ribosyl) transferase (MART) PARP14 in ovarian cancer cells. MARylation of RACK1 is required for stress granule formation and promotes the colocalization of RACK1 in stress granules with G3BP1, eIF3{eta}, and 40S ribosomal proteins. In parallel, we observed reduced translation of a subset of mRNAs, including those encoding key cancer regulators (e.g., AKT). Treatment with a PARP14 inhibitor or mutation of the sites of MARylation on RACK1 blocks these outcomes, as well as the growth of ovarian cancer cells in culture and in vivo. To re-set the system after prolonged stress and recovery, the ADP-ribosyl hydrolase TARG1 deMARylates RACK1, leading to the dissociation of the stress granules and the restoration of translation. Collectively, our results demonstrate a therapeutically targetable pathway that controls stress granule assembly and disassembly in ovarian cancer cells. SummaryWe have discovered a druggable PARP14/TARG1-regulated pathway that mediates site- specific mono(ADP-ribosyl)ation of RACK1, a ribosomal protein. This pathway controls stress granule assembly and disassembly, as well as the translation of a subset of mRNAs, to modulate the growth of ovarian cancer cells in culture and in vivo.

cell biology↗

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

The early development and physiology of Xenopus laevis tadpole lateral line system

Xenopus laevis has a lateral line mechanosensory system throughout its full life cycle. Previous studies of the tadpole lateral line system revealed that it may play a role in escape behaviour. In this study, we used DASPEI staining to reveal the location of tadpole lateral line neuromasts. Destroying these neuromasts with neomycin resulted in loss of escape responses in tadpoles. We then studied the physiology of anterior lateral line in immobilised tadpoles. Activating the neuromasts behind one eye could evoke asymmetrical motor nerve discharges when the tadpole was resting, suggestive of turning/escape, followed by fictive swimming. When the tadpole was already producing fictive swimming however, anterior lateral line activation reliably led to the termination of swimming. The anterior lateral line had spontaneous afferent discharges at rest, and when activated showed typical adaptation. There were also efferent activities during tadpole swimming, the activity of which was loosely in phase with ipsilateral motor nerve discharges, implying modulation by the motor circuit from the same side. Calcium imaging experiments located sensory interneurons in the primary anterior lateral line nucleus in the hindbrain. Future studies are needed to reveal how sensory information is processed by the central circuit to determine tadpole motor behaviour. Summary statementActivating tadpole anterior lateral line evokes escape responses followed by swimming and halts ongoing swimming. The afferent and efferent activities and sensory interneuron locations in the hindbrain are reported.

neuroscience↗

bioRxiv2019

Two different pathways for initiation of Trichoderma reesei Rad51-only meiotic recombination

BackgroundMeiotic recombination is mainly, but not exclusively, initiated by Spo11-induced double strand breaks (DSBs) in some sexual eukaryotes. DSBs are repaired by one or two RecA-like recombinases (ubiquitous Rad51 and meiosis-specific Dmc1). In yeast and mammals, Dmc1 is superior to Rad51 in tolerating mismatched sequences during highly polymorphic hybrid meiosis. The mechanisms underlying Rad51-only meiotic recombination remain less studied.\n\nResultsThe Rad51-only filamentous fungus Trichoderma reesei has only one spo11 gene. Removal of spo11 from T. reesei genome does not affect normal sexual development, meiosis or chromosome synapsis, but results in decrease of interhomolog recombination products to 70%, crossover homeostasis and lower genetic interference. Our results also suggest that T. reesei Rad51, like yeast and mammalian Dmc1 (but not Rad51), can tolerate mismatched sequences during meiotic recombination. Moreover, Topoisomerase II might act redundantly (and predominantly) with Spo11 to initiate meiotic recombination.\n\nConclusionWe suggest that T. reesei is an emerging model for studying Spo11-independent and Rad51-only meiosis.

genetics↗

bioRxiv2017

Trichoderma reesei Complete Genome Sequence, Repeat-Induced Point Mutation And Partitioning Of CAZyme Gene Clusters

Trichoderma reesei (Ascomycota, Pezizomycotina) QM6a is a model fungus for a broad spectrum of physiological phenomena, including plant cell wall degradation, industrial production of enzymes, light responses, conidiation, sexual development, polyketide biosynthesis and plant-fungal interactions. The genomes of QM6a and its high-enzyme producing mutants have been sequenced by second-generation-sequencing methods and are publicly available from the Joint Genome Institute (JGI). While these genome sequences have offered useful information for genomic and transcriptomic studies, their limitations and especially their short read lengths make them poorly suited for some particular biological problems, including assembly, genome-wide determination of chromosome architecture and genetic modification or engineering. We integrated Pacific Biosciences and Illumina sequencing platforms for the highest-quality genome assembly yet achieved, revealing seven telomere-to-telomere chromosomes (34,922,528 bp; 10877 genes) with 1630 newly-predicted genes and >1.5 Mb of new sequences. Most new sequences are located on AT-rich blocks, including 7 centromeres, 14 subtelomeres and 2329 interspersed AT-rich blocks. The seven QM6a centromeres separately consist of 24 conserved repeats and 37 putative centromere-encoded genes. These findings open up a new perspective for future centromere and chromosome architecture studies. Next, we demonstrate that sexual crossing readily induced cytosine-to-thymine point mutations on both tandem and unlinked duplicated sequences. We also show by bioinformatic analysis that Trichoderma reesei has evolved a robust repeat-induced point mutation (RIP) system to accumulate AT-rich sequences, with longer AT-rich blocks having more RIP mutations. The widespread distribution of AT-rich blocks correlates genome-wide partitions with gene clusters, explaining why clustering of genes has been reported to not influence gene expression in Trichoderma reesei. Compartmentation of ancestral gene clusters by AT-rich blocks might promote flexibilities that are evolutionarily advantageous in this fungus soil habitats and other natural environments. Our analyses, together with the complete genome sequence, provide a better blueprint for biotechnological and industrial applications.

genomics↗