Biology subjects

Joo, Y.

Publications and source records attributed to Joo, Y..

5 recordsLinked to original sources

bioRxiv2026

Regulation of protein kinase pathways in primary neuron model of anti-NMDA receptor encephalitis.

The most common form of autoimmune encephalitis is associated with antibodies that target N-methyl-D-aspartic acid receptors (NMDARs). NMDARs play a pivotal role in neurotransmission and synaptic plasticity. Mounting evidence has shown that antibody targeting of the NMDAR GluN1 subunit, as in anti-NMDAR encephalitis, leads to NMDAR cross-linking and receptor internalization. However, the underlying signaling pathways affected by antibodies targeting NMDARs remain to be explored. We previously demonstrated that a human GluN1 monoclonal antibody 5F5 (GluN1 mAb 5F5) rapidly localizes to and regulates synaptic NMDAR function at native synapses of primary hippocampal neurons. Here, we sought to explore signaling targets of GluN1 mAb 5F5 in primary cortical neurons of either sex using subcellular fractionation, Western blotting, and label-free quantitative phosphoproteomics by mass spectrometry. We find that human GluN1 mAb 5F5 does not change NMDAR abundance or surface levels of GluN1 on primary cortical neurons at 2 hr. Despite this, we observe that GluN1 mAb 5F5 alters the phosphoproteome in synaptoneurosomes and regulates numerous synapse-related biological processes and protein kinase activities. Bioinformatic analyses suggest that these phosphoproteomic changes are positively correlated with NMDAR activation and negatively correlated with NMDAR inhibition. Together, these data suggest that GluN1 mAb 5F5 alters intracellular kinase signaling pathways in primary cortical neurons, likely by activating the NMDAR. These studies may help to identify novel therapeutic strategies for anti-NMDAR encephalitis and other antibody-mediated encephalitides targeting cell surface antigens.

neuroscience↗

bioRxiv2026

Shoot loss reveals the latent capacity of Arabidopsis roots to reconstruct the plant body

Plant body organization depends on the coordinated development and function of shoots and roots, yet their functional specialization and interdependence remain incompletely understood. Whereas shoot senescence and death, as well as root regeneration from shoot tissues, are well studied, what capacities roots retain in the absence of the shoot remain unclear. To address this question, we tracked Arabidopsis roots after complete shoot excision. Initially, the remaining roots entered a growth-arrested but viable state. Despite broad repression of growth-associated programs, auxin and cytokinin signaling persisted, and the roots retained developmental responsiveness. This arrested state, however, was not developmentally terminal. By approximately 20 days after excision, green structures emerged from lateral root-associated domains. They accumulated chlorophyll and starch, assimilated carbon in response to light, and developed persistent cuticle-covered surfaces. Based on their origin and shoot-like characteristics, we termed them lateral root-derived shoots (LRSs). LRSs arose preferentially in the most shoot-proximal region, where cytokinin signaling progressively accumulated. Excision of this region repositioned LRS formation to the newly established proximal boundary, indicating spatial redefinition of shoot-forming competence. Auxin and cytokinin antagonistically governed the choice between continued lateral root growth and LRS identity, with cytokinin further promoting leaf-like differentiation. LRSs subsequently formed roots and developed into fertile plants under appropriate conditions. These findings reveal that roots retain developmental competence after shoot loss and can reorganize positional and hormonal programs to acquire shoot identity and reconstruct a complete plant body.

plant biology↗

bioRxiv2026

eCOMET: An R package for evaluating metabolic diversity and enrichment from LC-MS/MS data to test ecological hypotheses from individuals to ecosystems

O_LIMethods in metabolomics have grown exponentially in recent years, providing new insight into the ecological function and evolutionary impact of diverse plant metabolites. Metabolomics requires a command of numerous tools, the outputs of which are typically integrated through in-house, custom code that presents a workflow bottleneck and a barrier to entry for researchers in ecology, evolution, and behavior who may benefit from adding a metabolomics perspective to their research. C_LIO_LIWe introduce eCOMET, an R package for integrating and harmonizing the outputs of common metabolomics bioinformatics tools and conducting statistical analyses and data visualization methods useful for ecological metabolomics. C_LIO_LIOur package combines metabolome feature metadata with quantification tables (e.g., mzmine), feature dissimilarity matrices (e.g., modified cosine and DreaMS), and feature annotations (e.g., SIRIUS) into a cohesive R data object to facilitate downstream analyses, including the calculation of diversity and disparity metrics and differential accumulation analysis. C_LIO_LIOur goal is to make metabolomics accessible to a wider range of researchers in ecology, evolution, and behavior to unlock the potential of ecological metabolomics to generate novel insight in these fields. C_LI

ecology↗

bioRxiv2025

CREG1 promotes autophagy and protects the heart against nutritional stress-induced injury and age-associated hypertrophy, fibrosis and diastolic dysfunction

BackgroundCellular repressor of E1A-stimulated genes 1 (CREG1) is an evolutionarily conserved endolysosomal glycoprotein that enhances lysosomal biogenesis and autophagy, suppresses proliferation, and promotes differentiation. A prior gene targeting strategy that produced truncated N-terminal fragments resulted in embryonic lethality, limiting the ability to assess the physiological role of complete CREG1 loss. We hypothesized that CREG1 regulates cardiac autophagy, thereby maintaining cardiac structure and function under both physiological and stress conditions. MethodsWe generated true Creg1 knockout (KO) mice by deleting the entire open reading frame and established a gain-of-function model by inserting human CREG1 into the Rosa26 locus. Cardiac structure and function were assessed in global and cardiomyocyte-specific Creg1 knockout (cmCreg1KO) and knock-in (cmCREG1KI) mice. Autophagy was evaluated using biochemical assays, immunofluorescence, electron microscopy, and the CAG-EGFP-RFP-LC3 reporter analysis. ResultsGlobal Creg1 knockout mice developed progressive cardiac hypertrophy, fibrosis, and diastolic dysfunction at [~]80 weeks of age. At younger ages, CREG1 deficiency increased susceptibility to nutritional stress, resulting in mitochondrial damage and myofiber disruption in cardiomyocytes. cmCreg1KO mice exhibited dilated cardiomyopathy, left atrial thrombosis, and lethality around 50 weeks of age; however, interpretation of disease severity is confounded by Myh6-Cre-associated cardiotoxicity, which may mask additional pathogenic effects attributable to CREG1 loss. In contrast, cmCREG1KI mice demonstrated enhanced exercise capacity under nutritional stress. Mechanistically, CREG1 was localized to endolysosomal and autophagosomal compartments. Loss of CREG1 impaired autophagy flux and mitophagy, likely due to defective autophagosome membrane expansion and degradation. In contrast, CREG1 overexpression enhanced autophagy in cardiomyocytes. ConclusionsCREG1 is a key regulator of cardiac autophagy, protecting the heart against nutritional stress-induced injury and age-associated cardiac hypertrophy, fibrosis, and diastolic dysfunction. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/687936v1_ufig1.gif" ALT="Figure 1000"> View larger version (60K): org.highwire.dtl.DTLVardef@1b9fc05org.highwire.dtl.DTLVardef@150e48aorg.highwire.dtl.DTLVardef@1cc47adorg.highwire.dtl.DTLVardef@75ed53_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

Properties of individual hippocampal synapses influencing NMDA-receptor activation by spontaneous neurotransmission.

NMDA receptor (NMDAR) activation is critical for maintenance and modification of synapse strength. Specifically, NMDAR activation by spontaneous glutamate release has been shown to mediate forms of synaptic plasticity as well as synaptic development. Interestingly, there is evidence that within individual synapses each release mode may be segregated such that postsynaptically there are distinct pools of responsive receptors. In order to examine potential regulators of NMDAR activation due to spontaneous glutamate release in cultured rat hippocampal neurons, we utilized GCaMP6f imaging at single synapses in concert with confocal and super-resolution imaging. Using these single spine approaches, we found that Ca2+ entry activated by spontaneous release tends to be carried by GluN2B-NMDARs. Additionally, the amount of NMDAR activation varies greatly both between synapses and within synapses, and is unrelated to spine and synapse size, but does correlate loosely with synapse distance from the soma. Despite the critical role of spontaneous activation of NMDARs in maintaining synaptic function, their activation seems to be controlled factors other than synapse size or synapse distance from the soma. It is most likely that NMDAR activation by spontaneous release influenced variability in subsynaptic receptor position, release site position, vesicle content, and channel properties. Therefore, spontaneous activation of NMDARs appears to be regulated distinctly from other receptor types, notably AMPARs, within individual synapses.\n\nSignificance StatementUnderstanding the underlying synaptic mechanisms for learning and memory is critically important to the field of neuroscience and for human health. A key neurotransmitter receptor type involved in learning is the NMDA receptor, and exploration of its regulation is vital. In this study, we optimized optical tools to allow detailed characterization of NMDA receptor activity at single synapses, along with analysis of structural features of the imaged synapses. The amount of receptor activation is independent of the size of the synapse, but weakly dependent on synapse position within the dendritic tree. Notably, we found that NMDA receptors activated following spontaneous neurotransmitter release tend be GluN2B-containing receptors. Thus, the unique mechanisms that regulate the number and positioning of these receptors within synapses will have important consequences for control of synaptic development and signaling.

neuroscience↗