Biology subjects

Song, W.

Publications and source records attributed to Song, W..

At least 19 recordsLinked to original sources

bioRxiv2026

Information contracts determine what inverse perturbation benchmarks measure

Inverse perturbation benchmarks rank interventions toward a desired cellular state, but high accuracy can answer a different question from biological prioritization. We present InverseBench, which makes candidate information and endpoint construction explicit, and FSTN, a linear pipeline evaluated under it. With identical inputs, candidates and validation, nested ridge reaches Spearman 0.959 for a transcriptional principal-component proxy but 0.445 for independently measured K562 growth fitness across 7,354 genes. Controlled response-entry availability across seven tasks gives heterogeneous gains, 0.442 for CD4 activation and 0.116 for external fitness. Yet predefined shortlist comparisons show no primary-cutoff penalty in K562 or a melanoma co-culture screen, and secondary cutoffs reverse the K562 ordering. FSTN's nonnegative set selector recovers 0.840 of measured two-gene constituents in three picks, against 0.771 for an unconstrained greedy. The framework separates proxy reconstruction, response-informed prioritization and unseen-intervention ranking: an endpoint-dependent accuracy gap does not by itself mean worse biological decisions.

bioinformatics↗

bioRxiv2026

DeepD enables efficient genome modeling and controllable long-context sequence generation across domains of life

Genome foundation models hold great potential for advancing biological research, but modeling diverse complex genomes and generating controllable genome-scale sequences remain challenging. We present DeepD, a phylogeny-informed sparse mixture-of-experts model operating at single-nucleotide resolution over a 1-million-token context while reducing active computation. Pretrained on unselected whole-genome sequences across all domains of life, DeepD learns genic and intergenic sequence features and supports broad sequence-to-function prediction across species. DeepD performs well in human protein fitness and disease variants effect prediction, such as BRCA1 and BRCA2, with particular strength in regulatory regions, such as promoter and transcription-factor binding sites. Expert routing captures exon-intron boundaries, transposable elements, and distal cis-regulatory elements. DeepD also generates experimentally validated core promoters with specified transcriptional strengths. Finally, the Context-Anchor-Body strategy enables generation of complete yeast chromosome sequences and megabase-scale Arabidopsis segments, preserving gene structure and order while introducing variations within natural ranges. Together, DeepD is an efficient genome foundation model that unifies accurate sequence-to-function prediction with controllable genome-scale generation, advancing predictive and generative design of complex genomes.

bioinformatics↗

bioRxiv2026

Reversion to the Meta Body Form of Life after Complete Cell Death in Pure Liquid Water

The prevailing view holds that simpler animate beings predating the dawn of cellular life once existed, yet they have long since vanished from the present-day Earth. Our hypothesis posits that these animate beings persist to this day. To this end, we devised a long-term experiment spanning over a decade, keeping Staphylococcus aureus (S. aureus) within a sealed aqueous system of pure water. The findings illustrated that, upon the complete cell death (CCD) of the S. aureus, as cellular remnants progressively succumbed to dissolution, the aqueous solution underwent self-purification, bringing forth a class of lipid bilayer membrane microspheres containing RNA and proteins. These structures maintained long-term sustainable stability within the thermodynamic storm of water molecules and underwent dynamic size fluctuations over time - collectively exhibited phenomena indicative of being "alive". This study reveals that the cell, upon complete cell death, undergoes reversion to a living entity simpler than the cell itself - the Meta Body (MB). The discovery of MB opens an entire re-conceptualization of what death ultimately brings.

biophysics↗

bioRxiv2026

Grow2Fold: mapping heterogeneous developmental growth to human brain folding

Cortical folding emerges through complex developmental processes, yet what organizes these processes into the characteristic folding patterns of the human brain remains unclear. Here, we developed an imaging-informed whole-brain modeling framework, Grow2Fold, that integrates developmental cortical regionalization, quantitative growth characterization, and mechanics-guided simulation to investigate how cortical growth shapes brain folding patterns. Using 836 fetal and neonatal MRI sessions from 747 participants spanning 21-45 postmenstrual weeks, we identified a reproducible and hierarchical spatiotemporal organization of cortical expansion characterized by coordinated regional growth trajectories. Rapid expansion occurs earlier around peri-central territories and progressively shifts toward frontal, parietal, and temporal association cortices. We encoded these imaging-derived trajectories into region- and age-specific growth laws and incorporated them into anatomically realistic whole-brain mechanical models. The resulting simulations recapitulate major sulcal landmarks and characteristic folding development across global and regional morphological measures. Comparing regional and uniform growth, we find that differential growth drives cortical instability, while heterogeneous developmental growth organizes this instability into anatomically recognizable folding patterns. Combined with subject-specific anatomy, these population-informed growth laws reproduce individualized longitudinal folding trajectories. Together, our results identify spatiotemporally patterned developmental growth as a key spatial constraint on cortical morphogenesis and establish a quantitative bridge from developmental imaging, through mechanical instability, to anatomically organized folding.

biophysics↗

bioRxiv2026

Microbial valerate is associated with CAR T dysbiosis and its supplementation enhances CAR T function in B-cell lymphoma

Anaerobe-depleting antibiotic exposure is associated with inferior progression-free survival after CD19 CAR T-cell therapy in large B-cell lymphoma, yet the cellular mechanisms linking gut dysbiosis to the CAR T-cell product and whether this imprint is reversible have remained undefined. In two independent CAR-T candidate cohorts, low stool valerate at the time of CAR-T eligibility identified a multi-metabolite-deficient dysbiotic gut microbiome state marked by depletion of fiber-fermenting commensals and loss of carbohydrate-fermentation, SCFA-biosynthesis, and amino-acid metabolism pathways. Reanalysis of single-cell RNA sequencing from 42 lymphoma patients stratified by piperacillin-tazobactam/imipenem/meropenem (PIM) exposure revealed that PIM-exposed CAR T-cell products were CD4-skewed, with significantly elevated AP-1/immediate-early gene (IEG) and cellular activation signatures that together predicted inferior progression-free survival. Ex vivo conditioning of CAR T-cells with valerate produced a chromatin and transcription factor program distinct from butyrate or propionate, characterized by KLF/SP/EGR family engagement, KLF4 promoter opening, and broad induction of AP-1/IEG and MHC class II transcripts, whereas butyrate drove broader chromatin remodeling with TBX21/EOMES/NF-{kappa}B gains and KLF2 promoter closure, and propionate induced an NFY-centered program with preferential commitment to low-mitochondrial-content states. Untargeted metabolomics confirmed valerate uptake and mitochondrial {beta}-oxidation in CAR T-cells, while dietary sodium valerate supplementation in meropenem-treated mice bearing A20 lymphoma significantly reduced tumor burden and extended survival compared with CAR T-cells alone. These findings identify stool valerate as a bedside-deployable biomarker of dysbiosis-imprinted CAR T-cell dysfunction and support ex vivo or dietary valerate supplementation as a clinically tractable strategy to improve CAR-T anti-tumor function in patients with disrupted gut microbiomes.

cancer biology↗

bioRxiv2026

Cross-Species Comparison of Topologically Associating Domains (TADs) in Cereals Reveals Their Role in Genome Stability During Evolution

Topologically associating domains (TADs) are essential structural and functional modules of the genome that play a crucial role in regulating gene expression. In this study, we systematically investigated the conservation and evolution of TADs in five closely related crops, including maize, sorghum, coix, foxtail millet and broomcorn millet. Our results show that 74% of TAD boundaries are conserved between two inbred maize lines, B73 and Mo17, and that approximately 50% or more of TAD boundaries are conserved across different crop species. TAD number remains relatively stable in the face of changes in genome size. However, the length of TADs varies depending on genome size. Furthermore, we found that large-scale transposable element expansion leads to TAD expansion, while chromosomal inversions lead to TAD fusion and the formation of new TAD boundaries. Frequent chromatin interactions between subgenome chromosomes occur after whole-genome duplication. Moreover, we also found that crossovers are enriched at TAD boundaries in maize, indicating the importance of TADs as a fundamental unit during species evolution. Overall, our study provides insights into the conservation and evolution of TADs in crop genomes and their roles in genome organization and function.

plant biology↗

bioRxiv2026

Seeing the world in a grain of sand: Fine global and local representations in foveal and parafoveal vision

Foveal vision enables primates to perceive small objects with remarkable precision by resolving both fine-global form and fine-local detail. Yet current coarse-to-fine and local-to-global frameworks, derived largely from parafoveal recordings and large-object representations, posit that V1 encodes local detail whereas IT represents global form, leaving the neuronal basis of foveal object representation unresolved. Here we show that fine-global form and fine-local detail are encoded parallelly as early as V1 and preserved across V2, V4 and IT at both foveal (1{degrees}-2{degrees}) and parafoveal (2{degrees}-6{degrees}) retinal eccentricities. Coarse-global features dominate parafoveal vision and higher cortical areas. Response latencies revealed a rapid processing sequence, with 2-6 ms separating coarse-global, fine-local, and fine-global processing within parafoveal V1, V2 and V4. These findings establish a cortical neuronal framework to resolve fine-global form of small objects in foveal vision along primate ventral visual stream, supporting fine-scale perception during reading and fine object recognition. Highlights O_LIFoveal two-photon imaging across V1, V2, V4, and IT C_LIO_LIGlobal and local processing examined across eccentricity C_LIO_LIFine and coarse global representations emerge as early as V1 C_LIO_LIFine global and local representations are preserved from V1 up to IT C_LIO_LITightly timed coarse-to-fine-to-fine processing within each cortex C_LIO_LIFast coarse-global dominates parafoveal and higher cortical areas C_LI

neuroscience↗

bioRxiv2026

Incorporation of single-neuron projectome-based connectivity motifs enhances the cortex-specific performance of artificial neural networks

The organizational principles of natural neural networks could inspire the new architecture design of artificial neural networks (ANNs). Analysis of single-neuron connectomes of mouse brains revealed distinct profiles of three-node connectivity motifs in various cortical areas and hippocampal formation. A connectome-informed neural network algorithm ("CINA") was developed to incorporate natural connectivity motifs into ANN algorithms represented by recurrent neural network (RNN) and transformer-based large language model (LLM). We found that incorporation of the average profile of cortical motifs improved the RNNs performance in noise-resistant categorization and motor learning benchmark tasks, as compared with RNNs with random connectivity. Notably, incorporating cortex-specific motifs further elevated the RNNs performance in tasks related to the cortical function, and this effect was enhanced by artificially increasing the bias in the motif profile. Similar experimental results were verified on an LLM using Motif-Transformer for natural language question answering and brain-signal decoding tasks. Graph-theoretic analyses showed that incorporating natural motifs drove the emergence of modular and small-world properties in ANNs. Together, we demonstrated not only connectome-inspired optimization of ANN architecture but also functional significance of specific motif profiles in various cortices.

neuroscience↗

bioRxiv2026

Conserved TIR-only proteins drive transcriptional defense and basal immunity in dicot and monocot plants

Toll/interleukin-1/resistance (TIR) domain NADase enzymes signal in plant immunity by producing ribosylated nucleotide second messengers which activate EDS1 dimer-helper NLR pathways to restrict pathogen growth. Members of a small, distinctive group of TIR-only proteins are conserved between dicots and monocots, yet their functions remain poorly understood. Here, we show that conserved TIR-only proteins in Arabidopsis and barley share a fundamental enzymatic role in promoting basal defense against virulent filamentous pathogens, independently of NLR mediated effector-triggered immunity. Metabolite analysis of transiently expressed Arabidopsis and barley TIR-only proteins revealed their capacity to produce ribosylated cyclic nucleotides in vivo. By comparing phenotypes of tir-only and eds1 pad4 CRISPR mutants in the two species, as well as adr1 mutants in barley, we established that the TIR-only proteins promote PAMP-triggered transcriptional defenses associated with pathogen restriction. Barley possesses just one essential TIR-only enzyme and mutations of the two conserved TIR-only members in Arabidopsis were not compensated for by numerous other TIR-domain genes in the basal immune response. These findings suggest that conserved TIR-only proteins make a crucial contribution to TIR basal defense signaling networks of Arabidopsis and barley. We propose that a shared function in transcriptional defense regulation could explain the evolutionary retention of this discrete TIR-only group across monocot and dicot lineages.

plant biology↗

bioRxiv2026

WTAP-mediated epitranscriptomic program in alveolar macrophages confers prolonged protection against postinfluenza bacterial pneumonia

Secondary bacterial infections remain an intractable problem of seasonal influenza, primarily due to the depletion and defunctionalization of alveolar macrophages (AMs). Here, we described that N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, critically orchestrates trained immunity (TRIM) establishment in AMs. Influenza A virus (IAV)-trained AMs maintained low Wilms tumor 1-associated protein (WTAP) expression and reduced global m6A deposition for over two months. Mechanistically, this IAV-induced m6A decrease promotes TRIM by enhancing the RNA stability of phagocytic and metabolic genes, thereby boosting antibacterial function. Mimicking this m6A reduction pharmacologically or genetically recapitulates the IAV-trained TRIM phenotype, which improves phagocytosis and protects mice from secondary infection. Clinically, elevated WTAP in AMs correlates with impaired phagocytosis and disease severity in COVID-19 and COPD. These findings for the first time unveil how respiratory virus infection shapes AM TRIM via epitranscriptomic reprogramming, and offer prospective strategies for the prevention and treatment of post-viral bacterial complications.

immunology↗

bioRxiv2026

DNA-induced conformational changes in SPRTN relieve its auto-inhibitory effect on protease activity

The DNA-dependent metalloprotease SPRTN has emerged as a key enzyme in the proteolysis of DNA-protein crosslinks (DPCs), thereby protecting us against genome instability, accelerated ageing, and cancer. DNA and ubiquitin chains serve as the primary activator and catalyst of SPRTN proteolysis, respectively, but how they promote SPRTN activation and activity remains incompletely understood. To address this question, we developed a highly sensitive multi-turnover fluorescence resonance energy transfer (FRET) assay to monitor SPRTN proteolysis in real time. We found that the auto-cleaved N-terminal SPRTN fragment, comprising the metalloprotease domain (MPD), zinc-binding domain (ZBD), and basic region (BR), is highly stable, enzymatically active, and retains ubiquitin-dependent activation. Interestingly, the MPD alone exhibits basal intrinsic activity that is independent of both DNA activation and ubiquitin avidity effect. We show that ZBD and MPD together exert steric regulation: ZBD maintains MPD in an autoinhibited state, while MPD largely prevents ZBD from binding DNA. BR, together with DNA, is essential to relieve ZBD-mediated inhibition of MPD. Using a site-trapping approach, we demonstrate that the ZBD-BR-DNA trinity induces an open conformation of the SPRTN N-terminus in cis, thereby releasing autoinhibition. MPD and BR together restrict the DNA-binding stoichiometry of ZBD, enabling SPRTN to function efficiently in proximity to DNA despite its low abundance in vivo. Collectively, our work overturns the long-standing dogma that SPRTN autocleavage inactivates the enzyme and reveals how DNA-induced conformational changes in SPRTN fine-tune its protease activity, providing a prerequisite for subsequent ubiquitin activation and rapid proteolysis of DPCs.

biochemistry↗

bioRxiv2026

Generation and long-term expansion of human pancreatic islet organoids in vitro

The scarcity of expandable, functional human islet cells remains a major barrier to diabetes therapy. Here, we identify PROCR+ cells within adult human islets and establish a defined culture system to generate pancreatic islet organoids. These organoids self-organize into -, {beta}-, {delta}-, and PP cells at near-native ratios, exhibit regulated insulin and glucagon secretion, and support exponential in vitro expansion. Single-cell transcriptomics reveals a unique progenitor-like cell population that is transcriptionally primed for endocrine differentiation but shares molecular features with fetal trunk cells and endocrine progenitors. When transplanted, the organoids rapidly ameliorate hyperglycemia in diabetic mice. Importantly, in a non-human primate model, intraportal transplantation of these organoids reduced exogenous insulin requirements, restored glucose-stimulated C-peptide secretion, and achieved sustained glycemic control-representing a critical step toward clinical translation. This study provides a strategy for expanding human islet organoids, offering a scalable platform for diabetes treatment, disease modeling, and regenerative medicine.

cell biology↗

bioRxiv2026

Heterogeneous transmission estimation and strategy optimization for Chikungunya: a vector-borne modeling study differentiating age and sex

Against the backdrop of global climate change and accelerating population mobility in 2025, chikungunya fever (CHIKF) exhibited a trend of worldwide spread, significantly increasing the difficulty of controlling tropical mosquito-borne diseases. To enhance the precision of intervention strategies, this study developed an age- and sex-structured human-mosquito interaction dynamic model based on data from the largest CHIKF outbreak ever recorded in China, and conducted a targeted analysis of prevention and control strategies. By decomposing the basic reproduction number and examining population heterogeneity, asymptomatic males aged 15-59 years were identified as the core transmission group. Optimal control analysis revealed that the synergistic implementation of three measures-- reducing the effective human-to-mosquito transmission rate, reducing the effective mosquito-to-human transmission rate, and suppressing mosquito population density--could reduce the overall infection rate by 95.7586%. Among these, mosquito population suppression should be prioritized as a universal core strategy; however, its protective effect on females aged 60 years and above was relatively weak, warranting particular attention. The study further demonstrated that asymmetric intensity combinations targeting these three intervention pathways--such as intensity profiles of "10%, 90%, 90%" or "60%, 80%, 90%"--could achieve effective outbreak control. This research elucidates population-specific transmission patterns and key pathways for intervention intensity, providing a theoretical and strategic foundation for the precise control of mosquito-borne diseases. It also provides actionable operational insights to support rapid response and strategy optimization for future emerging outbreaks. Author summaryCHIKF is a mosquito-borne viral disease that is gradually spreading from tropical regions to other areas. To achieve more precise control of this disease, we developed an age- and sex-structured analytical model based on the largest CHIKF outbreak in China, aiming to provide a scientific basis for responding to potential future outbreaks with inherent uncertainties. The study found that asymptomatic males aged 15-59 years were the primary drivers of transmission and should be prioritized as a key population for reducing viral spread in prevention efforts. When evaluating the effectiveness of different intervention strategies, females aged 60 years and above were the least affected by the implemented measures, indicating that this group should strengthen personal protection to lower their infection risk. Among all control measures, mosquito suppression was the most effective, suggesting that vector control strategies should be prioritized in future outbreak responses.

pathology↗

bioRxiv2026

Interactome mapping in human excitatory neurons reveals novel risk genes and pathways in Alzheimer's disease

Alzheimers disease (AD) is an irreversible neurodegenerative disease defined by its molecular hallmarks - amyloid beta peptide plaques and neurofibrillary Tau tangles. Despite significant progress that has been made in uncovering a large number of genetic risk factors through extensive genomic sequencing and genetic studies, the molecular mechanisms driving AD-associated pathology and cognitive decline remain poorly understood. Therefore, alongside the identification of more risk genes, it is also paramount to study how these genes function and influence each other within the cellular pathways and overall molecular networks in AD-relevant brain cell types. However, current human protein-protein interactome datasets were all generated in either yeast or generic human cell lines. Consequently, many important neuronal interactions, especially neuron-specific ones, have yet been discovered. To address this critical gap, we developed a highly scalable, high-quality interactome mapping pipeline in human excitatory neurons derived from induced pluripotent stem cells (iPSC), and generated a comprehensive, neuron-specific interactome map, named ADNeuronNet, for key AD risk genes. ADNeuronNet consists of 1,767 high-confidence interactions among 1,189 proteins and is the only dataset enriched with neuron-specific genes when compared to known protein interactions, including previous large-scale interactome maps, for the same baits in the literature. Within ADNeuronNet, we identified 1,375 novel interactions, many of which are likely neuron specific. For example, we identified a neuron-specific interactor, RIN2, for major AD risk factor BIN1 and confirmed RIN2s function in recruiting BIN1 to RAB5 positive early endosomes, a process that has been well-associated with AD etiology. Additionally, we performed quantitative interaction perturbation analyses on AD risk genes with AD-associated mutations or isoforms and identified significant changes in 99 protein interactions among 11 different protein variants. Finally, we found that subunits from the anaphase-promoting complex/cyclosome (APC/C), another novel BIN1 interactors identified by ADNeuronNet, mediated modulation of Tau-aggregation in neurons via regulation of APOE expression, uncovering a previously unrecognized BIN1-APC/C-APOE regulatory axis in AD pathobiology. In summary, these findings illustrate how our neuron-specific ADNeuronNet can be leveraged to uncover new risk gene candidates and cellular pathways that help advance our understanding of molecular mechanisms underlying AD etiology.

systems biology↗

bioRxiv2026

Fructose utilization by GM-CSF-differentiated macrophages aggravates autoimmune inflammation via MG-derived AGE-RAGE signaling

Excessive fructose intake is increasingly associated with metabolic and inflammatory pathologies; however, the direct impact of fructose metabolism on immune cell function remains insufficiently understood. Here, we demonstrate that GM-CSF-differentiated macrophages markedly upregulate the fructose-specific transporter GLUT5, enabling efficient fructose utilization through two complementary metabolic pathways. Using 13C-fructose tracing, we identified distinct carbon fluxes via a hexokinase (HK)-dependent glycolytic route and a ketohexokinase (KHK)-ALDOB-mediated fructolytic route. The HK-dependent pathway sustains glycolytic activity under glucose-limiting conditions, stabilizing HIF-1 and preserving pro-inflammatory gene expression. Conversely, the KHK-ALDOB axis increases dihydroxyacetone phosphate (DHAP) production, leading to methylglyoxal-derived advanced glycation end-products (MG-AGEs) that engage receptor for AGE (RAGE) signaling. This activation enhances MMP9 expression in macrophages and drives Th17 differentiation in CD4 T cells, amplifying inflammatory and tissue-remodeling processes. In vivo, fructose intake exacerbates autoimmune arthritis in SKG mice, and elevated fructose-driven glycolysis and MG-AGE accumulation are observed in monocytes from patients with rheumatoid arthritis. These results link fructose-driven carbonyl stress to macrophage effector programs and downstream T cell polarization. Collectively, these findings uncover a dual fructose metabolic program that integrates nutrient stress with persistent inflammation via the MG-AGE-RAGE axis and underscore the immunometabolic risks of excessive fructose exposure.

immunology↗

bioRxiv2025

IGHV3-53 antibody abundance drives divergent SARS-CoV-2 immune imprinting

The mechanisms driving divergent SARS-CoV-2 immune imprinting in populations with distinct SARS-CoV-2 exposure histories remain unclear. However, conventional wild-type mouse models fail to recapitulate severe imprinting, even after potent ancestral-strain mRNA immunization, hindering imprinting-related mechanistic investigation and vaccine evaluation. Here, we surprisingly found that V(D)J-humanized mice could faithfully recapitulate human severe imprinting phenotypes. Comprehensive antibody repertoire analysis and deep mutational scanning-based epitope mapping of 583 monoclonal antibodies from these models revealed that the pre-existing IGHV3-53/66 antibody abundance determine imprinting severity through antibody-mediated masking of Omicron-specific epitopes. Both passive IGHV3-53/66 antibody transfer and IGHV3-53 knock-in were sufficient to induce severe imprinting in wild-type mice. Together, these findings demonstrate that the V(D)J germline repertoire--even a single germline-encoded antibody response--can profoundly shape humoral imprinting severity. Accordingly, we established an IGHV3-53 knock-in mouse model that accurately recapitulates the human antibody landscape, providing a valuable tool for guiding future COVID-19 vaccine updates.

immunology↗

bioRxiv2025

Nucleophagy removes cytotoxic trapped PARP1

Poly (ADP-Ribose) Polymerase inhibitors (PARPi) induce cytotoxicity in homologous recombination repair (HRR)-deficient cancers by causing PARP1 to become trapped on chromatin, resulting in irreparable replication-associated DNA damage. Although increased clearance of trapped PARP1 from chromatin reduces the sensitivity of cancer cells to PARPi, details surrounding this process remain unclear. PARPi exposure is known to cause increased autophagy flux, whilst autophagy inhibition can hypersensitise cells to PARPi. Using various biochemical, cell biological and live imaging-based assays, we found that trapped PARP1 is cleared by nucleophagy, the selective autophagy of nuclear substrates. Specifically, the nucleophagy of trapped PARP1 was orchestrated by the selective autophagy receptor TEX264 and its partner segregase p97/VCP. TEX264 mediates this process by directly interacting with trapped PARP1, thus bridging PARP1 to the autophagosomal resident protein LC3 for processing via autophagy. Impeding this process, either chemically or genetically, heightened PARP1 trapping, leading to accumulation of protein aggregates, replication-associated DNA damage and cell lethality, re-sensitising PARPi-resistant cells to various PARPi. In conclusion, we show that nucleophagy acts in a cytoprotective manner to directly target PARPi-induced trapped PARP1 for degradation.

cell biology↗

bioRxiv2025

The functional divergence of two ethylene receptor subfamilies that exhibit Ca2+-permeable channel activity

Ethylene is a gaseous plant hormone crucial for regulating plant growth, development, and stress adaptation, yet the molecular basis underlying ethylene receptor function remains elusive. Here, we show that subfamily I receptors constitute core ethylene-sensing module and function epistatically to subfamily II receptors. Notably, we discover that only subfamily I receptors possess Ca2+-permeable channel activity, which are indispensable for ethylene-induced cytosolic calcium influx. Overall, this work supports a mechanistic framework in which subfamily I receptors integrate ethylene sensing with Ca2+ influx, providing new insight into how plants translate hormonal cues into downstream signaling events.

plant biology↗