Biology subjects

Kim, H.

Publications and source records attributed to Kim, H..

At least 271 records · Page 15Linked to original sources

bioRxiv2024

Response eQTLs, chromatin accessibility, and 3D chromatin structure in chondrocytes provide mechanistic insight into osteoarthritis risk

Osteoarthritis (OA) poses a significant healthcare burden with limited treatment options. While genome-wide association studies (GWAS) have identified over 100 OA-associated loci, translating these findings into therapeutic targets remains challenging. Integrating expression quantitative trait loci (eQTL), 3D chromatin structure, and other genomic approaches with OA GWAS data offers a promising approach to elucidate disease mechanisms; however, comprehensive eQTL maps in OA-relevant tissues and conditions remain scarce. We mapped gene expression, chromatin accessibility, and 3D chromatin structure in primary human articular chondrocytes in both resting and OA-mimicking conditions. We identified thousands of differentially expressed genes, including those associated with differences in sex and age. RNA-seq in chondrocytes from 101 donors across two conditions uncovered 3782 unique eGenes, including 420 that exhibited strong and significant condition-specific effects. Colocalization with OA GWAS signals revealed 13 putative OA risk genes, 10 of which have not been previously identified. Chromatin accessibility and 3D chromatin structure provided insights into the mechanisms and conditional specificity of these variants. Our findings shed light on OA pathogenesis and highlight potential targets for therapeutic development. Highlights{circ} Comprehensive analysis of sex- and age-related global gene expression in human chondrocytes revealed differences that correlate with osteoarthritis {circ}First response eQTLs in chondrocytes treated with an OA-related stimulus {circ}Deeply sequenced Hi-C in resting and activated chondrocytes helps connect OA risk variants to their putative causal genes {circ}Colocalization analysis reveals 13 (including 10 novel) putative OA risk genes

genetics↗

bioRxiv2024

Cholesterol Metabolite 27-Hydroxycholesterol Enhances the Secretion of Cancer Promoting Extracellular Vesicles by a Mitochondrial ROS-Induced Impairment of Lysosomal Function

Extracellular vesicles (EVs) serve as crucial mediators of cell-to-cell communication in normal physiology as well as in diseased states, and have been largely studied in regard to their role in cancer progression. However, the mechanisms by which their biogenesis and secretion are regulated by metabolic or endocrine factors remain unknown. Here, we delineate a mechanism by which EV secretion is regulated by a cholesterol metabolite, 27-Hydroxycholesterol (27HC), where treatment of myeloid immune cells (RAW 264.7 and J774A.1) with 27HC impairs lysosomal homeostasis, leading to shunting of multivesicular bodies (MVBs) away from lysosomal degradation, towards secretion as EVs. This impairment of lysosomal function is caused by mitochondrial dysfunction and subsequent increase in reactive oxygen species (ROS). Interestingly, cotreatment with a mitochondria-targeted antioxidant rescued the lysosomal impairment and attenuated the 27HC-mediated increase in EV secretion. Overall, our findings establish how a cholesterol metabolite regulates EV secretion and paves the way for the development of strategies to regulate cancer progression by controlling EV secretion.

cell biology↗

bioRxiv2024

Emergence of multiple foraging strategies under competition

Foraging strategies are shaped by interactions with the environment, and evolve under metabolic constraints. Optimal strategies for isolated and competing organisms have been studied extensively in the absence of evolution. Much less is understood about how metabolic constraints shape the evolution of an organisms ability to detect food and move through its environment to find it. To address this question, we introduce a minimal agent-based model of the coevolution of two phenotypic attributes critical for successful foraging in crowded environments: movement speed and perceptual acuity. Under competition higher speed and acuity lead to better foraging success, but at higher metabolic cost. We derive the optimal foraging strategy for a single agent, and show that this strategy is no longer optimal for foragers in a group. We show that mutation and selection can lead to the coexistence of two strategies: A metabolically costly strategy with high acuity and velocity, and a metabolically cheap strategy. Generally, in evolving populations speed and acuity co-vary. Therefore, even under metabolic constraints, trade-offs between metabolically expensive traits are not guaranteed.

evolutionary biology↗

bioRxiv2024

De novo design of protein minibinder agonists of TLR3

Toll-like Receptor 3 (TLR3) is a pattern recognition receptor that initiates antiviral immune responses upon binding double-stranded RNA (dsRNA). Several nucleic acid-based TLR3 agonists have been explored clinically as vaccine adjuvants in cancer and infectious disease, but present substantial manufacturing and formulation challenges. Here, we use computational protein design to create novel miniproteins that bind to human TLR3 with nanomolar affinities. Cryo-EM structures of two minibinders in complex with TLR3 reveal that they bind the target as designed, although one partially unfolds due to steric competition with a nearby N-linked glycan. Multimeric forms of both minibinders induce NF-{kappa}B signaling in TLR3-expressing cell lines, demonstrating that they may have therapeutically relevant biological activity. Our work provides a foundation for the development of specific, stable, and easy-to-formulate protein-based agonists of TLRs and other pattern recognition receptors.

biochemistry↗

bioRxiv2024

Mosaic display of stable hemagglutinin monomers induces broad immune responses

The nature of the interplay between immunity and viral variation is infinitely adaptive. Infection frequently induces immune responses against variation-prone epitopes, rather than against spatially hidden conserved epitopes. It thus remains a substantial challenge to elicit the immune responses to the conserved epitopes providing broad-spectrum immunity. We developed an approach of scaffold-mediated mosaic display to present monomeric influenza virus hemagglutinins (HAs), which exposes highly conserved stem and interface epitopes. Stable monomers were rationally engineered from H1 and H3 subtypes and B type HA trimers, with amino acid mutations at the monomer-monomer interface and for disulfide bond formation, and fused to a self-assembling scaffold, to generate a mosaic HA monomer-displaying nanoparticle, 3HA-np. Immunization with 3HA-np induced broadly neutralizing antibodies (bnAbs) in mice and ferrets and protected against challenges with H1N1 and H3N2 viruses. Competitive immunoassays revealed that 3HA-np induced high interface- and stem-binding Ab titers as compared to head Ab titers, indicating that the monomeric and mosaic nature of 3HA-np elicit cross-reactive Abs. Our results suggest that exposure of the hidden conserved epitope by monomer-displaying nanoparticles is a promising approach to generate a universal influenza vaccine.

bioengineering↗

bioRxiv2024

rRNA Operon Improves Species-Level Classification of Bacteria and Microbial Community Analysis Compared to 16S rRNA

Precise identification of species is fundamental in microbial genomics, crucial for understanding the microbial communities. While the 16S rRNA gene, particularly its V3-V4 regions, has been extensively employed for microbial identification, however has limitations in achieving species-level resolution. Advancements in long-read sequencing technologies have highlighted the rRNA operon as a more accurate marker for microbial classification and analysis than the 16S rRNA gene. This study aims to compare the accuracy of species classification and microbial community analysis using the rRNA operon versus the 16S rRNA gene. We evaluated the species classification accuracy of the rRNA operon,16S rRNA gene, and 16S rRNA V3-V4 region using a BLAST based method and a k-mer matching based method with public data available from NCBI. We further preformed simulations to model microbial community analysis. We accessed the performance using each marker in community composition estimation and differential abundance analysis. Our findings demonstrate that the rRNA operon offers an advantage over the 16S rRNA gene and its V3-V4 region for species-level classification within genus. When applied to microbial community analysis, the rRNA operon enables a more accurate determination of composition. Using the rRNA operon yielded more reliable results in differential abundance analysis as well. IMPORTANCEWe quantitatively demonstrated that the rRNA operon outperformed the 16S rRNA and its V3-V4 regions in accuracy, for both individual species identification and species-level microbial community analysis. Our findings can provide guidelines for selecting appropriate markers in the field of microbial research.

microbiology↗

bioRxiv2024

Rat primary cortical cell tri-culture to study effects of amyloid-beta on microglia function

IntroductionThe etiology and progression of sporadic Alzheimers Disease (AD) have been studied for decades. One proposed mechanism is that amyloid-beta (A{beta}) proteins induce neuroinflammation, synapse loss, and neuronal cell death. Microglia play an especially important role in A{beta} clearance, and alterations in microglial function due to aging or disease may result in A{beta} accumulation and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of microglia, astrocytes and neurons in the same culture. Here, we employ a tri-culture model of rat primary neurons, astrocytes, and microglia and compare it to co-culture (neurons and astrocytes) and mono-culture enriched for microglia to study microglial function (i.e., motility and A{beta} clearance) and proteomic response to exogenous A{beta}. MethodsWe established cortical co-culture (neurons and astrocytes), tri-culture (neurons, astrocytes, and microglia), and mono-culture (microglia) from perinatal rat pups. On days in vitro (DIV) 7 - 14, the cultures were exposed to fluorescently-labeled A{beta} (FITC-A{beta}) particles for varying durations. Images were analyzed to determine the number of FITC-A{beta} particles after specific lengths of exposure. A group of cells were stained for {beta}III-tubulin, GFAP, and Iba1 for morphological analysis via quantitative fluorescence microscopy. Cytokine profiles from conditioned media were obtained. Live-cell imaging with images acquired every 5 minutes for 4 hours was employed to extract microglia motility parameters (e.g., Euclidean distance, migration speed, directionality ratio). Results and discussionFITC-A{beta} particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-A{beta} particles, as confirmed via epifluorescence and confocal microscopy. Adding FITC-A{beta} significantly increased the size of microglia, but had no significant effect on neuronal surface coverage or astrocyte size. Analysis of the cytokine profile upon FITC-A{beta} addition revealed a significant increase in proinflammatory cytokines (TNF-, IL-1, IL-1{beta}, IL-6) in tri-culture, but not co-culture. In addition, A{beta} addition altered microglia motility marked by swarming-like motion with decreased Euclidean distance yet unaltered speed. These results highlight the importance of cell-cell communication in microglia function (e.g., motility and A{beta} clearance) and the utility of the tri-culture model to further investigate microglia dysfunction in AD.

neuroscience↗

bioRxiv2024

In-situ microscopy-assisted meniscus-guided coating for highly sensitive reduced graphene oxide-based nanocomposite biosensor

Meniscus-guided coating provides great potential for fabricating the nanomaterial-based thin film into high-performance biomedical devices due to the strong relationship between its experimental parameters and the resulting structural properties. However, the complex leverages of various fluid dynamics phenomena hamper optimization of structural properties and device performances. This is due to the absence of in-depth analytical techniques to observe, interpret, and control the solidification process. In this work, we propose an analytical strategy based on the rheological properties of a rGO-based solution using computational fluid dynamics modeling and in situ high-speed microscopy. Through this, we reveal the principles of the solidification mechanism that creates a rGO-based nanocomposite in the form of highly- and evenly-wrinkled thin film and the experimental condition at which this mechanism occurs. The optimized thin film presents high electroconductivity, low chip-to-chip signal variation, and multiplexed electrochemical biosensing performance for three classes of antibodies related to the excessive enrichment of endoplasmic reticulum stress, with detection limits of picomolar levels. This optimizing technique can be universally applied to understanding various solution-based coating systems, and can streamline the production of large-area and high-quality nanocomposite biosensors.

bioengineering↗

bioRxiv2024

Journey to the center of the phage; revealing the ejectosome of Pectobacterium bacteriophage {Phi}M1

Podophages that infect gram-negative bacteria, such as Pectobacterium pathogen {Phi}M1, encode tail assemblies too short to extend across the complex gram-negative cell wall. To overcome this, podophages encode a large protein complex (ejectosome) packaged inside the viral capsid and correspondingly ejected during infection to form a transient channel that spans the periplasmic space. Here we describe the ejectosome of bacteriophage {Phi}M1 to a resolution of 3.32 [A] by single particle cryo-EM. The core consists of tetrameric and octameric ejection proteins which form a [~]1.5 MDa ejectosome that must transition through the [~]30 [A] aperture created by the short tail nozzle assembly that acts as the conduit for the passage of DNA during infection. The ejectosome forms several grooves into which coils of genomic DNA are fit before the DNA sharply turns and goes down the tunnel and into the portal. In addition, we reconstructed the icosahedral capsid and hybrid tail apparatus to resolutions between 3.04 [A] and 3.23 [A], and note an uncommon fold adopted by the dimerized decoration proteins which further emphasize the structural diversity of podophages. These reconstructions have allowed the generation of a complete atomic model of the {Phi}M1, uncovering two distinct decoration proteins and highlighting the exquisite structural diversity of tailed bacteriophages. Significance StatementThis study resolves the cryo-EM structure of bacteriophage {Phi}M1, which possesses several unique and interesting structural elements, including a pair of distinct decoration proteins that are underreported in tailed DNA phages. Significantly, we also report the internal ejectosome proteins of {Phi}M1, which are highly non-conserved with previously solved proteins to date and demonstrate the structural diversity of ejection proteins. The ejectosome reveals a DNA spooling phenomenon whereby the viral genome wraps around the ejectosome within the capsid, which has never been reported before. We provide a clear, step-by-step method for the technically challenging reconstruction of ejectosomes using standard, open-source software.

microbiology↗

bioRxiv2024

FABP4 as a Therapeutic Host Target Controlling SARS-CoV2 Infection

Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients. We demonstrate that loss of FABP4 function, by genetic or pharmacological means, reduces SARS-CoV2 replication and disrupts the formation of viral replication organelles in adipocytes and airway epithelial cells. Importantly, FABP4 inhibitor treatment of infected hamsters diminished lung viral titers, alleviated lung damage and reduced collagen deposition. These findings highlight the therapeutic potential of targeting host metabolism in limiting coronavirus replication and mitigating the pathogenesis of infection.

microbiology↗

bioRxiv2024

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

ObjectiveElectronic (e-)cigarettes are the most used tobacco product amongst youth, and adult smokers favor e-cigarettes over approved cessations aids. Despite the lower perceived harm of vaping compared to smoking, inhalation of e-cigarette aerosol elicits cardiovascular responses that may lead to permanent injury when repeated over time. We thus aimed to infer the long-term outcomes of vaping on the function and structure of the aorta and shed light on the underlying cellular and molecular mechanisms. Approach and ResultsWe exposed female hypercholesterolemic mice to either pod-mod e-cigarette aerosol or room air daily for 24 weeks. Chronic inhalation of e-cigarette aerosol triggered accumulation of inflam-matory signals systemically and within aortic tissues, as well as T lymphocyte accrual in the aortic wall. Reduced eNOS expression and enhanced ROS production following eNOS uncoupling and NADPH oxi-dase activation curbed nitric oxide availability in the aorta of mice exposed to e-cigarette aerosol, impairing the endothelium-dependent vasodilatation that regulates blood flow distribution. Inhalation of e-cigarette aerosol thickened and stiffened aortic tissues via collagen deposition and remodeling, hindering the storage of elastic energy and limiting the cyclic distensibility that enables the aorta to function as a pressure reservoir. These effects combined contributed to raising systolic and pulse pressure above control levels. ConclusionsChronic inhalation of aerosol from pod-mod e-cigarettes promotes oxidative stress, inflammation, and fibrosis within aortic tissues, significantly impairing passive and vasoactive aortic functions. This evidence provides new insights on the biological processes that increase the risk for adverse cardio-vascular events as a result of pod-mod e-cigarette vaping.

bioengineering↗

bioRxiv2024

Discovery of Highly Active Kynureninases for Cancer Immunotherapy through Protein Language Model

Overcoming the immunosuppressive tumor microenvironment is a promising strategy in anticancer therapy. L-kynurenine, a strong immunosuppressive metabolite can be degraded through kynureninases. Through homology searches and protein language models, we identified and then experimentally determined the efficacy of four top-ranked kynureninases. The catalytically most active one nearly doubles turnover number over the prior best, reducing tumor weight by 3.42 times in mouse model comparisons, and thus, presenting substantial therapeutic potential.

cancer biology↗

bioRxiv2024

Nuclear pores as conduits for fluid flow during osmotic stress

Changing environmental conditions necessitate an immediate cellular adaptation to ensure survival. Dictyostelium discoideum, a bacteriovore slime mold present in the soil of most terrestrial ecosystems, is known for its ability to tolerate drastic changes in osmolarity. How the cells cope with the resulting mechanical stress remains understudied. Here we show that D. discoideum has extraordinarily elaborate and resilient nuclear pores that serve as conduits for massive fluid exchange between cytosol and nucleus. We capitalize on the unique properties of D. discoideum cells to quantify flow across the nuclear envelope that is necessitated by changing nuclear size in response to osmotic stress. Based on mathematical concepts adapted from hydrodynamics, we conceptualize this phenomenon as porous flow across nuclear pores. This type of fluid flow is distinct from the canonically characterized modes of nucleocytoplasmic transport, i.e. passive diffusion and active nuclear transport, because of its dependence on pressure. Our insights are relevant in any biological condition that necessitates rapid nuclear size changes, which includes metastasizing cancer cells squeezing through constrictions, migrating cells and differentiating tissues.

cell biology↗

bioRxiv2024

Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number

The brains remarkable properties arise from collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional "latent" signals reflecting neural computations. However, what would be the biological utility of such a redundant and metabolically costly encoding scheme and what is the appropriate resolution and scale of neural recording to understand brain function? Imaging the activity of one million neurons at cellular resolution and near-simultaneously across mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number. While half of the neural variance lies within sixteen behavior-related dimensions, we find this unbounded scaling of dimensionality to correspond to an ever-increasing number of internal variables without immediate behavioral correlates. The activity patterns underlying these higher dimensions are fine-grained and cortex-wide, highlighting that large-scale recording is required to uncover the full neural substrates of internal and potentially cognitive processes.

neuroscience↗

bioRxiv2024

Age-Related Decline in BBB Function is More Pronounced in Males than Females

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders. Significance statementThe blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.

neuroscience↗

bioRxiv2024

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations. In parallel, we describe a large population of stem-like alveolar tuft cells that express the endodermal stem cell markers Sox9 and Lgr5 and a receptor profile making them uniquely sensitive to cues produced by pleural Mesothelium. We hypothesized that crosstalk from mesothelial cells to alveolar tuft cells might be central to the regulation of post-penumonectomy lung regeneration. Following pneumonectomy, we find that mesothelial cells display radically altered phenotype and ligand expression, in a pattern that closely tracks with parenchymal epithelial proliferation and alveolar tissue growth. During an initial pro-inflammatory stage of tissue regeneration, Mesothelium promotes epithelial proliferation via WNT ligand secretion, orchestrates an increase in microvascular permeability, and encourages immune extravasation via chemokine secretion. This stage is followed first by a tissue remodeling period, characterized by angiogenesis and BMP pathway sensitization, and then a stable return to homeostasis. Coupled with key changes in parenchymal structure and matrix production, the cumulative effect is a now larger organ including newly-grown, fully-functional tissue parenchyma. This study paints Mesothelial cells as a key orchestrating cell type that defines the boundary of the lung and exerts critical influence over the tissue-level signaling state regulating resident stem cell populations. The cellular circuits unearthed here suggest that human lung regeneration might be inducible through well-engineered approaches targeting the induction of tissue regeneration and safe return to homeostasis.

systems biology↗

bioRxiv2023

Precise single-cell transcriptomic mapping of normal and leukemic cell states reveals unconventional lineage priming in acute myeloid leukemia

In acute myeloid leukemia (AML), genetic mutations distort hematopoietic differentiation, resulting in the accumulation of leukemic blasts. Yet, it remains unclear how these mutations intersect with cellular origins and whether they converge upon similar differentiation patterns. Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution mapping of the relationship between leukemia and normal cell states, yet this application is hampered by imprecise reference maps of normal hematopoiesis and small sample sizes among patient cohorts. As a first step we constructed a reference atlas of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states, that was benchmarked against independent datasets of immunophenotypically pure hematopoietic stem and progenitor cells. Using this reference atlas, we mapped over 1.2 million single-cell transcriptomes spanning 318 AML, mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) samples. This large-scale analysis, together with systematic mapping of genotype-to-phenotype associations between driver mutations and differentiation landscapes, revealed convergence of diverse genetic alterations on twelve recurrent patterns of aberrant differentiation in AML. This included unconventional lymphoid and erythroid priming linked to RUNX1 and TP53 mutations, respectively. We also identified non-genetic determinants of AML differentiation such as two subgroups of KMT2A-rearranged AML that differ in the identity of their leukemic stem cells (LSCs), likely reflecting distinct cellular origins. Furthermore, distinct LSC-driven hierarchies can co-exist within individual patients, providing insights into AML evolution. Together, precise mapping of normal and malignant cell states provides a framework for advancing the study and disease classification of hematologic malignancies thereby informing therapy development.

cancer biology↗

bioRxiv2023

An RXLR effector targets ER-Golgi interface to induce ER stress and necrotic cell death

To achieve successful colonization, the pathogen secretes hundreds of effectors into host cells to manipulate the hosts immune response. Despite numerous studies, the molecular mechanisms underlying effector-induced necrotic cell death remain elusive. In this study, we identified a novel virulent RXLR effector named Pc12 from P. capsici. Pc12 induces necrosis by triggering a distinct ER stress response through its interaction with Rab13-2. Unlike conventional hypersensitive response cell death associated with effector-triggered immunity, Pc12-induced cell death does not coincide with defense gene expression. Instead, it induces the aggregation of ER-resident proteins and confines secretory proteins within the ER. Pc12 interacts with Rab13-2, exhibiting a specific affinity for the active form of Rab13-2. Thus, the complex of Pc12 and Rab13-2 mimics the conformation of the inactive state of Rab13-2, subsequently recruiting the Rab-escort protein (REP). This process results in disruptions in vesicle formation within the ER-Golgi trafficking pathway. Furthermore, the substitution of a single amino acid of Rab13-2 structurally predicted to be crucial for the Pc12 interaction decreased the interaction with Pc12 while maintaining the interaction with REP1. These findings offer valuable insights into the ER stress-mediated cell death as well as a potential strategy for enhancing resistance against pathogens.

plant biology↗