Biology subjects

Molina, A.

Publications and source records attributed to Molina, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Yeast surface display reveals structure-dependent β-glucan association with the plant immune receptor AtIGP1

Cell wall-derived oligosaccharides can function as immune-active signals in plants and trigger pattern-triggered immunity (PTI) through pattern recognition receptors (PRRs). In Arabidopsis thaliana, the leucine-rich repeat malectin (LRR-MAL) receptor kinase IGP1 (impaired in glycan perception 1) contributes to immune responses induced by cellulose- and mixed-linkage {beta}-1,3/1,4-glucan (MLG)-derived oligosaccharides, although whether MLG-derived oligosaccharides are directly recognized by AtIGP1 needs further clarification. We established a Saccharomyces cerevisiae surface-display system in which the AtIGP1 extracellular domain (ECD) is presented at the yeast cell surface, allowing oligosaccharide recognition to be examined separately from downstream plant signaling and without receptor purification. Previously, cellulose-derived oligosaccharides have been shown to elicit plant defense responses via AtIGP1. Here, surface-displayed AtIGP1 retained the ability to recognize fluorescently labeled cellotriose (CEL3) and cellopentaose (CEL5) ligands, supporting functional presentation of the receptor for investigating glycan recognition in a heterologous context. Using this platform, we investigated the association of AtIGP1 with fluorescently labeled MLG-derived oligosaccharides differing in degree of polymerization (DP) and glycosidic linkage arrangement. This analysis revealed a specific, competitively displaceable association with MLG DP2 (G3G; laminaribiose), whereas the DP3 (G4G3G) and DP4 (G4G4G3G) structures tested showed no detectable association. To test whether this association is relevant in planta, we treated A. thaliana seedlings with unlabeled MLG DP2, which induced a cytosolic Ca2+ response, an early readout of immune activation. This response was markedly reduced in the igp1-3 mutant. Together, these results identify laminaribiose as an additional candidate ligand of AtIGP1. The established yeast surface-display platform thus provides an approach for testing candidate oligosaccharides for association with the extracellular domains of plant PRRs.

synthetic biology↗

bioRxiv2026

A pathogen α-L-arabinofuranosidase degrades host-derived immunogenic oligosaccharides to suppress plant immunity

Plant cell wall fragments released during pathogen attack can act as signalling molecules that trigger immune responses. Successful pathogens have potentially evolved diverse strategies to evade host recognition, including minimizing the accumulation of cell wall-derived elicitors. However, the mechanisms underlying this process remain largely unknown. Here, we characterized ZtGH54, an -L-arabinofuranosidase from the wheat pathogen Zymoseptoria tritici, that is essential for the acquisition of sugar nutrients from arabinan and arabinoxylan wall polysaccharides. ZtGH54 also hydrolyzes immunogenic oligosaccharides derived from arabinoxylan to prevent host recognition. Remarkably, this strategy is effective only in a subset of wheat cultivars, as the contribution of ZtGH54 to virulence is cultivar-dependent. While a ZtGH54 substrate is broadly recognized in wheat, one of the products generated by ZtGH54, xylotetraose, is recognized only by specific wheat cultivars, revealing natural variation in the perception of xylan-derived oligosaccharides. These findings establish ZtGH54 as a key virulence factor that simultaneously exploits cell wall host resources and suppresses wheat immunity through the precise hydrolysis of plant cell wall-derived signals.

plant biology↗

bioRxiv2026

Structural and functional insights into the role of Cysteine-Rich Receptor-Like Kinase 18 (CRK18) in Arabidopsis

Plants perceive and integrate diverse environmental signals through receptor kinase (RK) networks at the plasma membrane. Within this, Cysteine-Rich Receptor-Like Kinases (CRKs) constitute a large but not well-understood subfamily characterised by extracellular domains (ECDs) enriched in cysteine residues. CRKs have been implicated in plant responses to biotic and abiotic stress, as well as in developmental processes. Additionally, several CRKs have been proposed to act as redox sensors. Here, we investigate the homodimerization mechanism of Arabidopsis CRK18 and its regulation by redox conditions. By modulating pH and redox state, we assessed the stability and binding dynamics of the CRK18 ECD and its cysteine mutants. We also tested the plasma membrane localisation of all the cysteine mutants involved in the predicted disulfide bonds, and only CRK18C227A, C228A-ECD resembled the plasma membrane localization of wild-type CRK18. We combine co-immunoprecipitation, Forster resonance energy transfer-fluorescence lifetime imaging microscopy and microscale thermophoresis to quantify CRK18 self-association in planta and in vitro. Furthermore, we place CRK18 dimerization in a broader signalling context by identifying CRK18 interaction partners and CRK18-dependent signalling outputs. Using Arabidopsis CRK18 overexpression lines, we perform (phospho)proteomic and immunoprecipitation-mass spectrometry (IP-MS) analyses to map CRK18-centred signalling networks associated with stress-related responses. The constitutive activation of the CRK18 kinase domain and its interaction with many putative (cell wall) glycan-sensing RKs, including PERK15, suggest a regulatory role for CRK18. The absence of significant changes in the proteome and phosphoproteome of CRK18 overexpression lines in the absence of any trigger, and its restricted mobility after elicitation, suggest that CRK18 requires a stimulus for activation and possibly induces membrane microdomain reorganisation. This is in line with the infection assay with the nematode Heterodera schachtii, which causes modification and targeted damage to plant cell walls during infection, revealing that CRK18 acts as negative regulator of this process.

biochemistry↗

bioRxiv2026

Perturbation response decomposition enables biologically aligned generalization to unseen perturbations and cellular contexts

Predicting single-cell responses to genetic perturbations could reveal the vast combinatorial space of perturbations and cellular contexts that is infeasible to measure experimentally, yet current deep learning models generalize poorly and often fail to outperform simple baselines. Here we demonstrate that generalizability in perturbation prediction requires identifying and representing distinct components of cellular response rather than on increasing model complexity alone. We introduce a decomposition framework that explicitly separates transcriptional responses into global, perturbation-specific, cell-line-specific, and perturbation-by-cell-line interaction components. Applied to four CRISPR-interference Perturb-seq screens on multiple cell lines, our framework reveals that these components have distinct structures and information requirements. The global response component is low-dimensional, reflects recurrent proliferation and stress response programs, and can be inferred from control gene expression. In contrast, the perturbation and cell-line specific components are high-dimensional and cannot be recovered from control expression. We therefore develop response-component-aligned models that map biological priors, such as gene coessentiality, onto the geometry of observed transcriptional responses. Critically, this alignment enables simple linear or multilayer perceptron (MLP) based models to outperform state-of-the-art architectures across multiple generalization settings, including unseen cell lines and combinations of unseen perturbations. Together, our framework for response decomposition and alignment provides a principled basis for evaluating and designing perturbation-prediction models, showing that generalization depends primarily on matching biological information to the response components rather than on model complexity alone.

bioinformatics↗

bioRxiv2026

Dietary fiber intake associates with improved survival and microbiomecomposition in allogeneic hematopoietic cell transplantation

Diet is linked to changes in gut microbiota and metabolite production with clinical relevance in several disease settings, although these effects remain poorly defined. We performed prospective, real-time diet monitoring (37,929 food items, 3,837 patient days) and longitudinal microbiome and metabolite profiling (1,230 fecal samples) in a clinical cohort of 173 patients undergoing allogeneic hematopoietic cell transplantation. Patients with pre-transplant fiber intake above the cohort average had significantly improved overall survival (p=0.014) and reduced incidence of grades 2-4 acute graft-versus-host disease (GVHD) (p=0.032) post-transplant. Those consuming insoluble fiber had increased microbial diversity, enriched butyrate-producing taxa, and depleted Enterococcus. Those who developed lower gastrointestinal GVHD had reduced fecal butyrate levels. In a GVHD preclinical model, we confirmed that a fiber-enriched diet increased survival, cecal butyrate, and regulatory-to-conventional T cell ratio. Thus, we demonstrated that dietary fiber has clinical significance as a modifiable factor with microbiome-mediated effects.

cancer biology↗

bioRxiv2026

Future-proofing agrobiodiversity: climate and niche-aware conservation planning using reinforcement learning.

Despite substantial global commitments to expand protected-area networks, the strategic allocation of limited resources remains challenging. Spatial conservation planning helps identify priority regions that maximise conservation benefits per unit area. Yet, they also tend to neglect two fundamental aspects of conservation: climate-driven range shifts and the representation of environmentally distinct populations within species. Here, we propose a continental-scale conservation planning framework that explicitly accounts for both processes through novel routines implemented in the conservation planning software CAPTAIN. We apply this framework to European crop wild relatives (CWR), for which niche coverage is a focal priority, as it underpins their potential to support agricultural adaptation to future environmental stressors through breeding programs. Comparative analyses on a subset of 186 CWR associated with five focal crops show that accounting for range shifts and niche coverage leads to substantially different conservation priorities from those obtained with a baseline model based on current distributions only. These additions reduced the number of non-protected species by 64%, increased the average protected distribution range by 43%, increased mean niche coverage from 75.8% to 84.5% and reduced the number of species with less than half of their niche protected from 35 to 10. Applied to a more comprehensive checklist of 1,140 European CWRs, the final framework identifies continental-scale priority areas representing 93.5% of these taxa and includes 94.4% of its critically endangered species. Our results highlight the importance of incorporating both temporal dynamics and within-species environmental representation when designing conservation strategies under climate change. RepositoryThe repository will be made publicly accessible after publication at doi: https://10.5281/zenodo.19855597

ecology↗

bioRxiv2025

Genetic factors driving multi-host infection in a core member of the root mycobiota

Core members of the fungal root microbiota include pathogens capable of colonizing multiple hosts, yet the underlying genetic determinants remain unknown. We report that Plectosphaerella cucumerina is a core member of the Arabidopsis thaliana root microbiota displaying high pathogenic potential and multi-host colonization capabilities. Establishment of a Plectosphaerella reference culture collection, followed by whole-genome sequencing of 72 strains reveals subtle phenotypic and genotypic variation that associate with fungal phylogeny, but not host plant identity. Transcriptome profiling of a model P. cucumerina isolate in roots of multiple hosts identifies core and host-specific fungal processes linked to carbon catabolism and root cell wall deconstruction of the hosts. A fungal gene encoding a candidate {beta}-1,3-glucanase (GH64) was identified as a key genetic factor driving infection and disease in plants that diverged 110 million years ago. The gene is enriched in plant-colonizing fungi and consistently functions as a disease determinant in the root pathogen Colletotrichum incanum. We conclude that diverse and tunable fungal repertoires of carbohydrate-active enzymes act as disease determinants and drive multi-host compatibility belowground.

microbiology↗

bioRxiv2025

Evolutionary and geometric signatures reveal ligand-binding sites across proteomes

Identifying protein binding sites is central to drug discovery, yet many computational approaches still trade off precision, recall, or throughput when scaled. We introduce PickPocket, a deep learning model that fuses evolutionary information from protein sequences with geometric representations of structure to identify ligand-binding residues at proteome scale. By leveraging complementary sequence context and spatial neighborhoods, PickPocket generalizes across diverse protein families and ligand chemistries while operating at a recall-oriented setting with competitive precision. In benchmark evaluations it delivers strong residue-level recovery and, despite no explicit training on conformational switching, reliably identifies cryptic pockets in held-out structures, comparing favorably with specialized approaches. Applied across 356,711 proteins, the method nominates previously unannotated candidate sites enriched for functional signals and highlights tractable surface chemistry on therapeutically relevant targets. These results position evolutionary-geometric fusion as a practical foundation for large-scale site mapping that can shorten the path from structure to experiment and support hit discovery, mutagenesis design, and target assessment.

bioinformatics↗

bioRxiv2025

Glycan recognition by a plant sentinel immune receptor

Pathogens target and degrade the extracellular matrix surrounding plant cells. A central question is how cell wall-derived damage-associated molecular patterns (DAMPs) are recognized and integrated to trigger immune responses. We address this question by determining the structure of the multidomain receptor IGP1 in both apo form and bound to the cellulose-derived DAMP cellotriose. Structural analyses reveal that constitutive Leucine Rich Repeat-malectin interactions preconfigure IGP1 for ligand recognition and that the receptor features a highly specific sugar-binding pocket in the LRR domain capable of distinguishing fine variations in glycan structures. By directly sensing cello-oligomers, IGP1 acts as a cell wall sentinel that links pathogen-induced wall degradation to immune alerting, equipping plants to mount rapid and robust defense responses.

plant biology↗

bioRxiv2025

Efficient Design of Affilin(R) Protein Binders for HER3

Engineered scaffold-based proteins that bind to concrete targets with high affinity offer significant advantages over traditional antibodies in theranostic applications. Their development often relies on display methods, where large libraries of variants are physically contacted with the desired target protein and pools of binding variants can be selected. Herein, we use a combined artificial intelligence/physics-based computational framework and phage display approach to obtain ubiquitin based Affilin(R) proteins targeting the HER3 extracellular domain, a relevant tumor target. We demonstrate that the developed in silico pipeline can generate de novo Affilin(R) proteins with high experimental success rate using a small training set of sequences (<1000 sequences). The classical phage display yielded primary candidates with low nanomolar affinities. These binders could be further optimized by phage display and computational maturation alike. These combined efforts resulted in four HER3 ligands with high affinity, cell binding, and serum stability that have theranostic potential.

biochemistry↗

bioRxiv2023

Efficient and accurate sequence generation with small-scale protein language models

Large Language Models (LLMs) have demonstrated exceptional capabilities in understanding contextual relationships, outperforming traditional methodologies in downstream tasks such as text generation and sentence classification. This success has been mirrored in the realm of protein language models (pLMs), where proteins are encoded as text via their amino acid sequences. However, the training of pLMs, which involves tens to hundreds of millions of sequences and hundreds of millions to billions of parameters, poses a significant computational challenge. In this study, we introduce a Small-Scale Protein Language Model (SS-pLM), a more accessible approach that requires training on merely millions of representative sequences, reducing the number of trainable parameters to 14.8M. This model significantly reduces the computational load, thereby democratizing the use of foundational models in protein studies. We demonstrate that the performance of our model, when fine-tuned to a specific set of sequences for generation, is comparable to that of larger, more computationally demanding pLM.

bioinformatics↗

bioRxiv2023

EZH2 represses mesenchymal genes and upholds epithelial identity in breast cancer cells

Emerging studies support that the Polycomb Repressive Complex 2 (PRC2) regulates phenotypic changes of carcinoma cells by modulating their shifts among metastable states within the epithelial and mesenchymal spectrum. This new role of PRC2 in cancer has been recently proposed to stem from the ability of its catalytic subunit EZH2 to bind and modulate the transcription of mesenchymal genes during epithelial-mesenchymal transition (EMT) in lung cancer cells. Here, we asked whether this mechanism is conserved across different types of carcinomas. By combining TGF-{beta}-mediate reversible induction of epithelial to mesenchymal transition and pharmacological inhibition of EZH2 activity we demonstrate that EZH2 represses a large set of mesenchymal genes and favours the residence of breast cancer cells towards the more epithelial spectrum during EMT. In agreement, analysis of human patient samples support that EZH2 is required to efficiently repress mesenchymal genes in breast cancer tumours. Our results indicate that PRC2 operates through similar mechanisms in breast and lung cancer cells. We propose that PRC2-mediated direct transcriptional modulation of the mesenchymal gene expression program is a conserved molecular mechanism underlying cell dissemination across human carcinomas.

cancer biology↗

bioRxiv2022

A group of Arabidopsis thaliana Leucine Rich Repeat-Malectin Receptor Kinases are required for the activation of immune responses triggered by cellulose and mixed-linked glucan oligosaccharides

Plant immune system perceives through the extracellular ectodomains (ECDs) of Pattern Recognition Receptors (PRRs) a diversity of carbohydrate ligands from plant and microbial cell walls, which activate Pattern-Triggered Immunity (PTI). Among these ligands are oligosaccharides derived from mixed-linked {beta}-1,3/{beta}-1,4-glucans (MLGs, e.g., {beta}-1,4-D-(Glc)2-{beta}-1,3-D-Glc, MLG43) and cellulose (e.g., {beta}-1,4-D-(Glc)3, CEL3). The mechanisms of perception of carbohydrates by plants are poorly characterized, with the exception of that determining recognition of fungal chitin oligosaccharides (e.g., {beta}-1,4-D(GlcNAc)6, CHI6) that involves several PRRs with LysM-ECDs that function as receptor or co-receptors. Here, we describe the isolation and characterization of Arabidopsis thaliana mutants impaired in glycan perception (igp), which are defective in PTI activation mediated by MLG43 and CEL3, but not CHI6. igp1-igp4 are altered in receptor-like kinases [RLKs: AT1G56145 (IGP1), AT1G56130 (IGP2/3), and AT1G56140 (IGP4)] with Leucine-Rich-Repeat (LRR) and Malectin (MAL) domains in their ECDs. igp4 is a T-DNA insertional, loss of function mutant whereas igp1 and the allelic igp2/igp3 harbour point mutations (E906K and G773E, respectively) in their kinase domains, which impact their structure and surface electrostatic potential as revealed by in silico structural analyses. Notably, Isothermal Titration Calorimetry assays with purified ECD-RLKs showed that AT1G56145 binds with high affinity CEL3 (Kd = 1.19 {+/-} 0.03 M) and cellopentaose (Kd = 1.40 {+/-} 0.01 M), but not MLG43, supporting AT1G56145 function as a plant PRR for cellulose oligosaccharides. Our data suggest that these LRR-MAL RLKs are receptor/co-receptors of a novel mechanism of perception of cellulose and MLG-derived oligosaccharides and PTI activation in Arabidopsis thaliana. Significance StatementNew oligosaccharides that trigger plant immunity have been described recently, but the mechanisms of perception of these glycans are unknown. We describe here three Arabidopsis thaliana receptor kinases (AT1G56130, AT1G56140, and AT1G56145) with Leucine Rich Repeat (LRR) and Malectin (MAL) domains in their extracellular ectodomains (ECDs), which function as Pattern Recognition Receptors (PRRs) triggering immune response mediated by oligosaccharides from cellulose ({beta}-1,4-glucan) and mixed-linked {beta}-1,3/1,4-glucans (MLGs) of plant and microbial cell walls. The ECD-AT1G56145 binds cellulose oligosaccharides, but not MLGs, supporting its function as a novel receptor of carbohydrate ligands in plants. Our data indicate that these LRR-MAL-PRRs control a complex mechanism of oligosaccharides perception and immune activation that differs from that of fungal chitin oligosaccharides recognition which involves LysM-PRRs.

plant biology↗

bioRxiv2022

Collagen remodeling dictates pancreatic cancer bioenergetics and outcome through DDR1 activation or degradation

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic, aggressive cancer that frequently progresses by liver metastasis1. Cancer-associated fibroblasts (CAF), extracellular matrix (ECM), and type I collagen (Col I) support2-5 or restrain PDAC progression and may impede blood supply and nutrient availability6-8. The dichotomous role of the stroma in PDAC, and the mechanisms through which it influences patient survival and enables desmoplastic cancers escape nutrient limitation remain poorly understood. Here we show that matrix metalloprotease (MMP)-cleaved or intact Col I (cCol I and iCol I, respectively) exert opposing effects on PDAC bioenergetics, macropinocytosis (MP), tumor growth and liver metastasis. While cCol I activates DDR1 (discoidin domain receptor-1)-NF-{kappa}B-p62-NRF2 signaling to promote PDAC growth, iCol I triggers DDR1 degradation and restrains PDAC growth. Patients whose tumors are enriched in iCol I and low in DDR1 and NRF2 have improved median survival compared to those enriched in cCol I, DDR1 and NRF2. Inhibition of DDR1-stimulated NF-{kappa}B or mitochondrial biogenesis blocked tumorigenesis in wildtype mice but not in mice expressing MMP-resistant Col I. In summary, the diverse effects of tumor stroma on PDAC growth, metastasis, and patient survival are mediated through the Col I-DDR1-NF-{kappa}B-NRF2-mitochondrial biogenesis pathway, presenting multiple new opportunities for PDAC therapy.

cancer biology↗

bioRxiv2022

EZH2 endorses cell plasticity to carcinoma cells facilitating mesenchymal to epithelial transition and tumour colonization

Reversible transition between the epithelial and mesenchymal states are key aspects of carcinoma cell dissemination and the metastatic disease, and thus, characterizing the molecular basis of the epithelial to mesenchymal transition (EMT) is crucial to find druggable targets and more effective therapeutic approaches in cancer. Emerging studies suggest that epigenetic regulators might endorse cancer cells with the cell plasticity required to conduct dynamic changes in cell state during EMT. However, epigenetic mechanisms involved remain mostly unknown. Polycomb Repressive Complexes (PRCs) proteins are well-established epigenetic regulators of development and stem cell differentiation, but their role in different cancer systems is inconsistent and sometimes paradoxical. In this study, we have analysed the role of the PRC2 protein EZH2 in lung carcinoma cells. We found that besides its described role in CDKN2A-dependent cell proliferation, EZH2 upholds the epithelial state of cancer cells by repressing the transcription of hundreds of mesenchymal genes. Chemical inhibition or genetic removal of EZH2 promotes the residence of cancer cells in the mesenchymal state during reversible epithelial-mesenchymal transition. In fitting, analysis of human patient samples and tumour xenograft models indicate that EZH2 is required to efficiently repress mesenchymal genes and facilitate tumour colonization in vivo. Overall, this study discloses a novel role of PRC2 as a master regulator of EMT in carcinoma cells. This finding has important implications for the design of therapies based on EZH2 inhibitors in human cancer patients.

cancer biology↗

bioRxiv2020

G1 PHASE LENGTHENING DURING NEURAL TISSUE DEVELOPMENT INVOLVES CDC25B INDUCED G1 HETEROGENEITY.

While lengthening of the cell cycle and G1 phase is a generic feature of tissue maturation during development, the underlying mechanism remains still poorly understood. Here we develop a time lapse imaging strategy to measure the four phases of the cell cycle in single neural progenitor cells in their endogenous environment. Our results show that neural progenitors possess a great heterogeneity of the cell cycle length. This duration variability is distributed over all phases of the cell cycle, with the G1 phase being the one contributing primarily to cell cycle variability. Within one cell cycle, each phase duration appears stochastic and independent except for a surprising correlation between S and M phase. Lineage analysis indicates that the majority of daughter cells display longer G1 phase than their mothers suggesting that at each cell cycle a mechanism lengthens the G1 phase. We identify an actor of the core cell cycle machinery, the CDC25B phosphatase known to regulate G2/M transition, as an indirect regulator of the duration of the G1 phase. We propose that CDC25B acts via a cell to cell increase in G1 phase heterogeneity revealing a novel mechanism of G1 lengthening associated with tissue development.

developmental biology↗

bioRxiv2020

Arabidopsis cell wall composition determines disease resistance specificity and fitness

Plant cell walls are complex structures subject to dynamic remodeling in response to developmental and environmental cues, and play essential functions in disease resistance responses. We tested the specific contribution of plant cell walls to immunity by determining the susceptibility of a set of Arabidopsis cell wall mutants (cwm) to pathogens with different parasitic styles: a vascular bacterium, a necrotrophic fungus and a biotrophic oomycete. Remarkably, most cwm mutants tested (31/38; 81.6%) showed alterations in their resistance responses to at least one of these pathogens, in comparison to wild-type plants, illustrating the relevance of wall composition in determining disease resistance phenotypes. We found that the enhanced resistance of cwm plants to the necrotrophic and vascular pathogens negatively impacted on cwm fitness traits, like biomass and seed yield. Enhanced resistance of cwm plants is not only mediated by canonical immune pathways, like those modulated by phytohormones or Microbe-Associated Molecular Patterns, which are not de-regulated in all cwm tested. Pectin-enriched wall fractions isolated from cwm plants triggered immune responses in other plants, suggesting that wall-mediated defensive pathways might contribute to cwm resistance. Cell walls of cwm plants show a high diversity of composition alterations as revealed by glycome profiling that detect specific wall carbohydrate moieties. Mathematical analysis of glycome profiling data identified correlations between the amounts of specific wall carbohydrate moieties and disease resistance phenotypes of cwm plants. These data support the relevant and specific function of plant wall composition in plant immune response modulation and in balancing disease resistance/development trade-offs.

plant biology↗

bioRxiv2019

Arabidopsis phytochelatin synthase 1, but not phytochelatin synthesis, functions in extracellular defense against multiple fungal pathogens

Phytochelatin synthase (PCS) is a key component of heavy metal detoxification in plants. PCS catalyzes both the synthesis of the peptide phytochelatin from glutathione as well as the degradation of glutathione conjugates via peptidase activity. Here, we describe a hitherto uncharacterized role for PCS in disease resistance against plant pathogenic fungi. The pen4 mutant, which is allelic to cadmium insensitive 1 (cad1/pcs1) mutants, was recovered from a screen for Arabidopsis mutants with reduced resistance to the non-adapted barley fungal pathogen, Blumeria graminis f. sp. hordei. PCS1, which is found in the cytoplasm of cells of healthy plants, translocates upon pathogen attack and colocalizes with the PEN2 myrosinase on the surface of immobilized mitochondria. pcs1 and pen2 mutant plants exhibit a similar metabolic defect in the accumulation of pathogen-inducible indole glucosinolate-derived compounds, suggesting that PEN2 and PCS1 act in the same metabolic pathway. The function of PCS1 in this pathway is independent of phytochelatin synthesis and deglycination of glutathione conjugates, as catalytic-site mutants of PCS1 are still functional in indole glucosinolate metabolism. In uncovering a previously unknown function for PCS1, we reveal this enzyme to be a moonlighting protein important for plant responses to both biotic and abiotic stresses.

plant biology↗