Biology subjects

Xu, B.

Publications and source records attributed to Xu, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Astrocytic ablation of truncated TrkB receptors reduces amyloid plaques and prevents synaptic loss in 5xFAD mice

Brain-derived neurotrophic factor (BDNF) is essential for nervous system development and function and exerts its effects primarily through the tropomyosin receptor kinase B (TrkB). The Ntrk2 gene encodes a full-length receptor (TrkB.FL) and two truncated isoforms (TrkB.T1 and TrkB.T2, collectively TrkB.T) that lack the intracellular tyrosine kinase domain. TrkB.T is expressed predominantly in astrocytes and is thought to inhibit BDNF-TrkB.FL signaling by sequestering BDNF and forming signaling-deficient heterodimers with TrkB.FL. Here, we investigated whether selective ablation of astrocytic TrkB.T could ameliorate Alzheimer's disease (AD) pathology by enhancing endogenous BDNF-TrkB.FL signaling. Astrocyte-specific deletion of the Ntrk2 gene at 5 weeks of age reduced cortical TrkB.T expression by more than 80% without affecting TrkB.FL levels. TrkB.T ablation increased the size of Bassoon-positive presynaptic active zones, consistent with enhanced BDNF-TrkB.FL signaling. Remarkably, astrocytic TrkB.T ablation reduced {beta}-amyloid plaque burden by more than 60% in the cortex, hippocampus, and subiculum of 6-month-old 5xFAD mice, despite having no detectable effect on microgliosis or astrogliosis. Furthermore, TrkB.T ablation prevented reductions in the density and size of PSD-95-positive postsynaptic sites in the cortex and hippocampus of 5xFAD mice at 1 year old. Together, these findings identify astrocytic TrkB.T as an important regulator of amyloid pathology and synaptic integrity in an AD mouse model. Our results suggest that selectively reducing TrkB.T expression represents a promising therapeutic strategy to enhance endogenous neuroprotective BDNF-TrkB.FL signaling, reduce amyloid pathology, and preserve synaptic integrity in AD.

neuroscience↗

bioRxiv2026

Positive selection and structural disruption of KCNA5 by mutation in colorectal cancer

Ion channels regulate cell proliferation, survival and migration, but the functional consequences of many ion channel mutations in cancer are unknown, and electrophysiological characterisation at scale is impractical. Here we use the mutational landscape of colorectal adenocarcinoma as a functional filter to identify potassium channel mutations under selection. A dN/dS screen of 16 potassium channels expressed in the large intestine identified KCNA5 (Kv1.5) as the strongest candidate under positive mutational selection. These mutations cluster in the T1 tetramerisation, S1-S4 voltage-sensor and pore domains, yet avoid the selectivity filter, indicating that selection does not favour loss of conduction. Within the pore region, the observed mutations occupy a biophysical space distinct from known C-type inactivation, activation-gate and toxin-binding mutations. In the voltage sensor, mutations affect gating-charge arginines. In the T1 domain, mutations fall on inter-subunit interfaces conserved across the KCNA family, and saturation mutagenesis energy calculations predict that they destabilise subunit contacts or the folding of the domain. Molecular dynamics simulations of D166N and G128R show loss of coordinated interface dynamics and distortion of the local backbone, respectively. Transcriptomic analysis of KCNA5-mutant tumours shows reduced expression of cell-cycle, KRAS-related and inflammatory pathways, and we observe differences between transcriptional effects induced by T1 and S1-S4 domain mutations. These changes are not reproduced by low KCNA5 expression alone, consistent with an effect specific to the mutant protein. Together, these computational results highlight that KCNA5 is under mutational selection in colorectal adenocarcinoma, and that these mutations are likely functional and induce phenotypic effects on tumors.

cancer biology↗

bioRxiv2026

A PVH-to-parabrachial BDNF circuit mediates non-aversive feeding suppression

Parabrachial nucleus (PBN) CGRP neurons mediate aversive feeding suppression, but PBN circuitry governing homeostatic, non-aversive feeding suppression remains poorly understood. Here, we identify a circuit in which paraventricular hypothalamus (PVH) neurons innervate BDNF-expressing ventrolateral/dorsolateral PBN (vl/dlPBNBDNF) neurons, which project to multiple hypothalamic nuclei. Refeeding strengthens excitatory and weakens inhibitory synaptic transmission in LPBN-projecting PVH neurons and preferentially induced Bdnf and Fos in vl/dlPBNBDNF neurons compared with elPBNCGRP neurons, whereas noxious LPS preferentially activated elPBNCGRP neurons. Gain- and loss-of-function experiments demonstrated that vl/dlPBNBDNF neurons are sufficient and necessary for feeding suppression without inducing conditioned taste aversion and that this effect require BDNF-TrkB signaling. In addition to hypothalamic inputs, vl/dlPBNBDNF neurons receive dense inputs from major downstream targets of elPBNCGRP neurons. Thus, vl/dlPBNBDNF neurons define a non-aversive feeding-suppression circuit positioned to integrate hypothalamic homeostatic signals with aversive signals, thereby coordinating food intake with internal energy needs and potentially harmful physiological conditions.

neuroscience↗

bioRxiv2026

Stress-recovery dynamics reveal a separatrix in transcriptomic landscapes across organs and aging

Aging is often characterized statically as molecular profiles, but how these profiles may affect the capacity of systems to respond to the external environment remains elusive. We perturbed young and aged mice via transient sleep deprivation and profiled transcriptomes from six organs immediately after stress and following recovery. The same perturbation induced complex temporal dynamics for each gene in an organ- and age- dependent manner. A shape parameter distinguished genes that recovered toward control expression from those that continued to drift away during recovery. Transcriptomic vector fields were inferred from these transitions using neural ordinary differential equations, revealing distinct stability regimes across organ systems. Interestingly, that of testis from the young mice contained a separatrix bounding the region within which perturbed state can return toward control. These findings establish transient perturbation and recovery as a framework for probing age-dependent transcriptomic stability and identifying boundaries that determine whether a perturbed system can return.

systems biology↗

bioRxiv2026

Deep ancestral structure, admixture and peripheral persistence shape diversity in the Papilio bianor species complex

Rapid diversification can generate regional biodiversity through ancestral polymorphism, admixture, and ecological differentiation, while leaving complex genomic signals. We analysed whole-genome variation in 325 butterflies, including 166 individuals of the Papilio bianor species complex and six outgroup species, to reconstruct lineage relationships and demographic history. Nuclear genomic analyses recovered three major clades corresponding to the recognized species and placed the island lineage as sister to continental P. bianor. Analyses of 18,635 autosomal window trees revealed extensive genealogical discordance, with incomplete lineage sorting predominating among continental lineages and the strongest introgression signals involving island related ancestry. Demographic modelling supported early island continental divergence followed by continental diversification and ancient admixture. The best fitting fastsimcoal2 model inferred an admixed origin of the Eastern China lineage, while BPP analyses supported ancient island-related introgression into the Eastern China ancestor, Western Himalaya and southwestern Thailand. Peripheral populations exhibited pronounced genetic differentiation and distinct demographic histories; Western Himalaya additionally showed mitochondrial affinity with Yaeyama despite its placement within the Himalayan nuclear lineage. Together, these findings suggest that introgression among deeply differentiated ancestral populations and incomplete lineage sorting during rapid divergence jointly shaped lineage diversity in the P. bianor complex. This study provides an empirical framework for investigating how lineage diversity emerges rapidly during the early stages of speciation, particularly in groups with deep ancestral population structure.

evolutionary biology↗

bioRxiv2026

Out-of-sight partners: autonomous wearable supernumerary limbs for dynamic co-manipulation

Supernumerary robotic limbs (SLs) could extend human motor capabilities beyond the natural body, yet most demonstrations have been limited to simple, quasi-static tasks or direct teleoperation under visual control. Whether humans can safely and intuitively collaborate with autonomous SLs during complex, dynamic tasks remains unknown. We studied this question in a demanding assembly task requiring coordinated transport and handovers of a long object, which could not be completed by a single person. We developed a reconfigurable backpack platform mounting up to four high-payload robotic arms, together with safety-aware motion planning that generates human-compatible trajectories from task states without training data. Despite the SLs operating out of sight, participants adapted quickly, completed the task reliably, and reported low cognitive demand alongside high perceived safety and predictability. Kinematic and force analyses showed that control design governed both movement fluency and whole-body stability: faster limb motions yielded smoother interactions and shorter completion times, and a mirrored coordination strategy--in which one robotic limb counterbalanced the other--further shortened duration and reduced variability in left-right ground reaction force differences during co-manipulation. These results show that humans can integrate autonomous wearable limbs as out-of-sight partners in dynamic whole-body collaboration, and delineate behavioral and control principles underpinning fluency, stability, and usability in human augmentation.

bioengineering↗

bioRxiv2026

Sexual dimorphism of autism-like phenotypes in microglial eIF4E overexpression mice

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and interaction, and restricted interests or repetitive behaviors. ASD is approximately four times more prevalent in males than in females. In this study, we investigated whether sex hormones or sex chromosomes underlie the male bias in ASD susceptibility. Methods: We used the MG4E mouse model, in which microglial eIF4E overexpression produces robust male-biased ASD-like phenotypes. To distinguish the contributions of sex hormones and sex chromosomes, MG4E mice were crossed with four-core-genotype (FCG) mice carrying Sry gene manipulations, generating eight genotypes of experimental mice. Social interaction and repetitive behaviors were assessed using standard behavioral assays. Dendritic spine density was quantified in Thy1-GFP mice. Expression of estrogen receptors (ERs) and androgen receptor (AR) was examined in microglia isolated from control and MG4E mice. Results: Sex hormones, rather than non-Sry genes on sex chromosomes, are responsible for the male-biased deficits in social interaction and the increase in dendritic spine density. At postnatal day 14, ERs were undetectable in microglia, whereas ER expression was readily detected in neurons. Conclusions: These findings demonstrate that sex hormones are a major determinant of the increased susceptibility of males to ASD-like phenotypes in MG4E mice. The absence of ER expression in microglia suggests that sex hormones may act indirectly through hormone-responsive neurons to regulate microglia-neuron interactions during neurodevelopment.

genetics↗

bioRxiv2026

Temporal N-terminomics analysis reveals proteome remodeling following brensocatib-mediated cathepsin C inhibition in promyeloblast cells

Cathepsin C (CatC) is known to activate neutrophil serine proteases (NSPs) involved in innate immune function although its broader impact on cellular proteolytic networks remains poorly defined. Here, we characterized the proteolytic landscape of HL-60 neutrophil progenitor cells following treatment with the CatC inhibitor brensocatib. Activity-based probes confirmed sustained inhibition of CatC by brensocatib, accompanied by progressive suppression of downstream elastase-like protease activation over 16 h, 72 h, and 7 days. An enrichment-free N-terminomics workflow was used to compare control and brensocatib-treated HL-60 cells. Following prolonged CatC inhibition, NSPs were reduced in abundance, while lysosomal cathepsins and endogenous protease inhibitors increased. These findings are consistent with remodeling of the protease-antiprotease network. Cleavage site analysis identified a pronounced, time-dependent NSP-associated P1 cleavage signature enriched for Val, Thr, Ala, Ile, and Cys in control cells that was progressively lost following brensocatib treatment. We also identified established and candidate CatC-dependent cleavage events, together with proteolytic adaptations that emerged in the absence of CatC activity. Collectively, these findings demonstrate that CatC inhibition extends beyond suppression of canonical NSP activation to progressive remodeling of the broader protease-antiprotease network, providing new mechanistic insight into the cellular consequences of therapeutic CatC inhibition.

biochemistry↗

bioRxiv2026

Transthyretin Contributes to Hippocampal Blood-Brain Barrier Recovery Following Intestinal Inflammation, with Reduced Expression in Alzheimer's Disease

Background: The blood-brain barrier (BBB) is increasingly recognized as an active immunoregulatory interface that responds dynamically to systemic inflammation. As intestinal inflammation can influence brain homeostasis through the gut-brain axis, the endogenous mechanisms that preserve BBB integrity during gut-derived inflammatory stress remain poorly understood. Methods and Results: We combined dextran sulfate sodium-induced colitis, fecal microbiota transplantation, aged mice, APP/PS1 mice, human Alzheimer's disease (AD) brain tissue, single-cell RNA sequencing, in vivo BBB permeability assays, and gain- and loss-of-function approaches to investigate adaptive neurovascular responses to gut inflammation and their mechanism in maintaining BBB integrity. Intestinal inflammation induced a region-specific adaptive response characterized by increased hippocampal vascular remodeling and partial restoration of BBB integrity following the initial inflammatory insult. Single-cell transcriptomic analysis identified a transthyretin (TTR)-enriched vascular-associated microglial state accompanying these neurovascular changes. Functional studies demonstrated that TTR contributes to maintaining BBB integrity by promoting endothelial homeostasis and limiting endothelial endocytosis, consistent with modulation of FcRn-associated transport pathways. This adaptive neurovascular response was progressively attenuated in aged mice and APP/PS1 mice and was accompanied by reduced vascular TTR expression in human AD brains. Conclusion: These findings identify TTR as a contributor of adaptive neurovascular homeostasis during gut-derived neuroinflammation. Impairment of this homeostatic response with aging and AD may contribute to persistent BBB dysfunction and chronic neuroinflammation, highlighting neurovascular resilience as a potential therapeutic target.

neuroscience↗

bioRxiv2026

PalmLab: A Comprehensive Computational Platform for Systematic Annotation and Functional Interrogation of Protein Palmitoylation

Protein palmitoylation is a dynamic and reversible post-translational lipid modification with progressively recognized pathophysiological relevance in cancer and a range of human diseases. Current databases, however, predominantly catalog palmitoylation sites derived from isolated literature reports, and suffer from a conspicuous lack of systematic harmonization across publicly available mass spectrometry (MS)-based palmitoylome datasets, which severely impedes standardized annotation and cross-cohort comparative analyses. Here, we introduce PalmLab, an integrative computational platform that synergistically couples MS-based palmitoylome data curation with interactive, multi-dimensional analytical functionalities for both human and mouse proteomes. Through a unified and rigorously standardized bioinformatics pipeline, PalmLab enables systematic reanalysis of all published palmitoylome datasets, yielding a curated compendium of 15,968 human and 9,924 mouse MS-validated palmitoylated proteins, a quantitative increase that more than doubles the total entries available in existing public repositories. The platform further provides user-friendly, code-free analytical modules that support differential palmitoylation profiling, context-specific pattern visualization, protein-protein correlation network inference, mutation-palmitoylation association mapping, and sequence-based motif discovery. Collectively, PalmLab constitutes a comprehensive and openly accessible resource for systematic palmitoylome mining and functional interrogation of palmitoylation events, thereby facilitating the elucidation of palmitoylation-mediated regulatory circuits and aiding the prioritization of novel therapeutic targets in oncology. The platform is freely available at https://palmlab.intelligent-oncology.com.

bioinformatics↗

bioRxiv2026

Neonatal Muscle Tone Predicts Cerebellar Morphology Later in Development Without Mediating Autistic Traits

Background: Infant muscle tone reflects early central nervous system integrity and has been associated with later motor and cognitive development, including autism traits. The cerebellum regulates both motor control and higher-order socio-cognitive functions and has been repeatedly implicated in autism, but its role in linking infant muscle tone to adolescent autistic traits has not previously been studied in a large, prospective population cohort. Methods: We used data from the prospective Generation R Study. Infant muscle tone (hypotonia and hypertonia) was assessed via Prechtl examination, and third-trimester fetal transcerebellar diameter was measured using ultrasound n=6,842). Cerebellar morphology at ages 6, 10, and 14 years (n=4,861) was measured using structural MRI. Linear mixed-effects models tested associations between infant muscle tone and 35 anatomical and 10 functional cerebellar regions. Causal mediation models tested whether cerebellar volume mediated associations between infant muscle tone and adolescent autistic traits at age 14 (Social Responsiveness Scale). Results: Hypotonia predicted larger vermis IX volumes across childhood (beta=0.037, pFDR =0.043). Hypertonia showed an age-dependent association with left lateral lobule IX (beta=-0.0027, pFDR =0.041), with differences diminishing with age. Third-trimester transcerebellar diameter did not predict postnatal muscle tone. Given its significant main effect, vermis IX volume was tested as a mediator, but did not mediate the pathway to adolescent autistic traits. However, infant hypotonia showed a small direct association with elevated autistic traits at age 14, specific to girls (beta=0.0255, p=0.020). Conclusions: Infant muscle tone is associated with localized differences in cerebellar volumes. These associations are specific to vermal and left hemispheric lobule IX, a region commonly implicated in spinocerebellar postural control, axial stability, and higher-order sensorimotor integration. Furthermore, infant muscle tone was not predicted by prenatal cerebellar diameter, and cerebellar volumes did not mediate the association between infant hypotonia and adolescent autistic traits in our study. Future research should further investigate these findings in clinical populations, integrating longitudinal whole-brain, multi-modal imaging to clarify the association between infant muscle tone, the cerebellar functioning, and autistic traits.

neuroscience↗

bioRxiv2026

Spatial multi-omics analysis reveals vimentin-high macrophages-endothelial cells niche shapes CAFs heterogeneity in colorectal cancer metastasis

The spatial architecture of the tumor microenvironment (TME) is pivotal in the progression of colorectal cancer (CRC) liver metastasis. By applying high-plex spatial multi-omic mapping and neighborhood analysis to a discovery cohort of colorectal cancer primary tumor (PT) and paired liver metastases (LM), we identified a specialized vimentin-high macrophages-endothelial cells niche that orchestrates cancer-associated fibroblast (CAF) phenotypes. Mechanistically, in primary tumors, vimentin-high macrophages secrete INHBA to activate the ACVR2/TGF-{beta} axis in endothelial cells, driving CAFs toward a myCAF phenotype. Conversely, in liver metastases, these macrophages secrete CXCL9 to trigger the PI3K-Akt/NF-[kcy]B/CXCL12 cascade in endothelial cells, directing CAFs toward an iCAF state. Clinically, high niche activity predicts poor survival. Divergent endothelial signaling in primary versus metastatic lesions exposes site-specific stromal vulnerabilities for therapeutic targeting, with architectural features discernible from routine histopathology. These findings reveal a site-specific regulatory mechanism of the macrophage-endothelial niche, offering a novel and clinically significant biomarker for CRC prognosis.

cancer biology↗

bioRxiv2026

Chromatin-Assisted Targeting Enables Precise DNA Methylation Editing in Plants

Precise installation of DNA methylation at selected loci offers a powerful strategy for regulating gene expression without altering DNA sequence, but existing plant epigenome editors are constrained by limited efficiency, locus dependence, and genome-wide off-target methylation. Here, we developed SunTag-MQ1v variants incorporating TRBIP1, which promotes removal of the antagonistic H3K4me3 mark, and CHLAMY, an oligomerizing alpha crystalline domain protein from Chlamydomonas reinhardtii. TRBIP1 enhanced methylation and silencing at the Arabidopsis FWA promoter but caused widespread off-target methylation and severe developmental defects. Adding CHLAMY produced SunTag-CHLAMY-TRBIP1-MQ1v (designated as SunTag-NOVA), which successfully overcame the lethality and widespread off-target effects associated with direct TRBIP1-MQ1v fusions. We demonstrate that CHLAMY drives higher-order oligomerization of the editing complex, which enhances target specificity and mitigates off-target accumulation. SunTag-NOVA robustly installed DNA methylation and repressed transcription at the endogenous FWA, FT and TMM genes with minimal genome-wide off-target consequences. These results show that combining local chromatin modification with controlled effector assembly can improve targeted DNA methylation, and establish SunTag-NOVA as a specific epigenome-editing platform for plants.

plant biology↗

bioRxiv2026

BCIJelly: An integrated ecosystem for brain-computer interface research

Brain-computer interface (BCI) research relies on multistage computational pipelines, but progress has been slowed by fragmented data formats, heterogeneous decoder implementations and hardware-specific deployment toolchains. Here, we introduce BCIJelly, a unified ecosystem that standardizes 18 BCI datasets into AI-ready inputs and integrates 15 benchmark decoders, 80 reusable modules, automated architecture search (AAS) and hardware-aware neuromorphic deployment. Our AAS constructs task-specific decoders without manual design and extends into a large language model (LLM)-driven closed-loop mode supporting single-task, multitask and cross-species decoder design. A single-command pipeline compiles trained decoders for neuromorphic hardware, reducing power consumption by 30 to 50 times while preserving decoding performance. An interactive visualization software enables code-free exploration of neural recordings and decoding outputs. BCIJelly is validated across five BCI paradigms (motor, visual, speech, emotion and auditory) in humans, macaques and mice, providing an extensible ecosystem connecting data standardization, decoder development, systematic evaluation and hardware-aware deployment for BCI research.

neuroscience↗

bioRxiv2026

Endothelial ANGPT2 insufficiency impairs retinal vascularization with ROP-like neovascular tufts

ANGPT2 is widely recognized as a critical regulator of pathological neovascularization. By analyzing scRNA-seq data from neonatal retinas, we demonstrate that Angpt2 transcripts are highly enriched in tip cells relative to other endothelial subtypes, where Angpt1/4 expression is absent. However, mechanisms underlying ANGPT2 function at angiogenic fronts remain inadequately understood. Here, we show that endothelial Angpt2 deletion severely disrupted retinal vascularization, characterized by neovascular tufts and micro-hemorrhage. Similar angiogenic defects also occurred in the brain, but were less evident in other tissues examined. Mechanistically, ANGPT2 insufficiency attenuated retinal tip cell invasion with aberrant mural cell coverage, compromising sprouting into non-vascularized tissues. Retinal RNA-seq analysis revealed that transcripts associated with endothelial migration and junction assembly were reduced in Angpt2 mutants compared to littermate controls, while upregulated genes were enriched in hypoxia-responsive pathways and mural cell development. Notably, abnormal mural-tip cell associations were detected within 48 hours post-Angpt2 deletion, displaying also a hypoxia-driven transcriptomic signature. These closely resemble the vascular pathologies observed in human retinopathy of prematurity. In contrast, Angpt1 insufficiency or Angpt4 deficiency primarily affected venous morphogenesis. Collectively, our findings imply that ANGPT2 is essential for driving tip cell invasion during sprouting angiogenesis, and that its insufficiency triggers hypoxia-driven vascular anomalies.

developmental biology↗

bioRxiv2026

Move BeTween modAlities (MBTA) employs flow matching to predict single cell data modalities

Integrating diverse molecular modalities to obtain a comprehensive view of cellular identity remains a major challenge in single-cell biology. A fundamental but underappreciated obstacle is structural mismatch -- the phenomenon in which the neighborhood structure of a cell differs depending on which molecular modality is used to define it. Existing approaches typically embed modalities into a shared latent space, which actively erases the structural differences between modalities that make multimodal measurements scientifically valuable. Here we introduce Move BeTween modAlities (MBTA), the first framework explicitly designed to address structural mismatch. Rather than forcing modalities into a shared representation, MBTA maintains modality-specific latent spaces and connects them via flow matching, preserving the structural integrity of each modality while enabling accurate cross-modal translation. Across extensive benchmarks on multi-modal single-cell datasets, MBTA consistently outperformed existing methods, with the largest gains observed in datasets with pronounced structural mismatch. Applied to joint genomic and transcriptomic profiles of breast cancer patients, MBTA identified transcriptomic lineage relationships corroborated by genomic variation and outperformed state-of-the-art transcriptomics-based copy number inference methods. Extending this framework to mouse embryonic development, we reconstructed temporal trajectories jointly defined by gene expression and seven complementary epigenetic modalities. MBTA can connect any number of molecular readouts without erasing their individual character, serving as the computational foundation for assembling multi-layered portraits of cells.

bioinformatics↗

bioRxiv2026

Hologenomics of xylotrophic bivalves reveals a minimalist, remote-acting evolutionary strategy of wood digestion

Wood constitutes the largest reservoir of biogenic carbon on Earth, yet remarkably few animals can exploit it. While terrestrial wood-feeders like termites rely on highly diverse gut microbiomes, xylotrophic marine bivalves have evolved a fundamentally different approach: a spatially segregated system where intracellular gill symbionts produce enzymes that act remotely within a nearly sterile cecum. However, the genetic and evolutionary basis of this unique symbiosis remains largely elusive. Here, we integrate hologenomics, transcriptomics, and biochemistry of a shallow-water shipworm (Teredo navalis) and a deep-sea borer (Xyloredo sp.). We find that despite diverging approximately 147 million years ago and occupying drastically different habitats, these bivalves maintain a strictly conserved ancestral karyotype and a shared genomic architecture for wood digestion. Our models reveal a clear host-symbiont division of labor. The host genome is specialized for lignin modification and targeted enzyme transport, whereas a highly streamlined symbiont community is responsible for core polysaccharide degradation. Central to this minimalist strategy is a lineage-specific GH5-GH6 dual-catalytic enzyme. By sharing amino acids across proximal binding pockets, this fusion protein unites endo- and exo-cellulase activities, enabling highly synergistic cellulose cleavage without the need for complex microbial communities. Ultimately, our comparative analysis with terrestrial models demonstrates that these marine invertebrates achieve efficient biomass degradation not through microbial expansion, but through extreme functional streamlining and molecular innovation, offering a distinct evolutionary paradigm for marine carbon cycling.

evolutionary biology↗

bioRxiv2026

Lipid Imbalance Generates Golgi Whorls that Sequester Small GTPases

Small GTPases are generally viewed as organizers of organelle identity, with different families recruited to specific membranes by compartment-selective targeting mechanisms. Here, we identify a membrane state that reverses this relationship. Excessive peptide S-palmitoylation at Golgi generates multilamellar, filipin-poor whorls that recruit ARF, Rab, and Rho family GTPases normally associated with distinct cellular compartments. The whorls simultaneously excluded Golgi transmembrane residents, coat proteins, ER proteins, a GPI-anchored protein, and other palmitoylated proteins, demonstrating that they were selective membrane compartments rather than nonspecific protein aggregates. Preventing myristoylation of ARF6 or geranylgeranylation of Rab11a strongly reduced recruitment, whereas prenylation alone was insufficient, indicating recognition of a composite membrane-targeting code. Lowering cellular cholesterol promoted whorl formation, whereas cholesterol supplementation suppressed it. Chemically distinct lipid perturbations generated GTPase-positive Golgi whorls, suggesting convergence on a shared membrane-remodeling state. As whorls accumulated, endocytic recycling and anterograde trafficking declined, survival signaling decreased, and viability became poorly reversible. These findings show that lipid imbalance can redirect small GTPases across normal organelle boundaries, converting Golgi-derived membranes into selective sinks for trafficking regulators.

cell biology↗