Biology subjects

Song, Y.

Publications and source records attributed to Song, Y..

At least 145 records · Page 8Linked to original sources

bioRxiv2025

Tet3 Mediates O-GlcNAcylation-Induced Remyelination

The failure of oligodendrocyte precursor cells (OPCs) to generate mature oligodendrocytes represents a major hurdle impeding myelin repair. However, the cellular determinants for OPC differentiation and the pharmacological targets driving remyelination remain rudimentary. Here, we demonstrate that O-GlcNAcylation intrinsically drives remyelination, in which Tet3 is one downstream effector. Enhanced O-GlcNAcylation significantly promotes OPC differentiation, whereas conditional depletion of Ogt in OPCs seriously impairs myelin formation in the developing central nervous system (CNS). Intriguingly, O-GlcNAcylation in OPCs positively correlates with the myelin status, and enhanced O-GlcNAcylation dramatically accelerates remyelination. Proteomic analyses reveal a cohort of proteins uniquely O-GlcNAcylated in OPCs. Among these, Tet3 is exclusively O-GlcNAcylated in OPCs within CNS, which in turn modulates its demethylation activity, thereby regulating myelin gene expression and remyelination. Our findings highlight the crucial role of the Ogt-Tet3 axis in OPC differentiation and suggest O-GlcNAcylation as a druggable target for treating demyelinating diseases.

developmental biology↗

bioRxiv2025

Lipid nanoparticle delivery of siRNA to dorsal root ganglion neurons to treat pain

Sensory neurons within the dorsal root ganglion (DRG) are the primary trigger of pain, relaying activity about noxious stimuli from the periphery to the central nervous system; however, targeting DRG neurons for pain management has remained a clinical challenge. Here, we demonstrate the use of lipid nanoparticles (LNPs) for effective intrathecal delivery of small interfering RNA (siRNA) to DRG neurons, achieving potent silencing of the transient receptor potential vanilloid 1 (TRPV1) ion channel that is predominantly expressed in nociceptor sensory neurons. This leads to a reversible interruption of heat-, capsaicin-, and inflammation-induced nociceptive conduction, as observed by behavioral outputs. Our work provides a proof-of-concept for intrathecal siRNA therapy as a novel and selective analgesic modality.

neuroscience↗

bioRxiv2025

Intraductal Papillary Mucinous Neoplasm Cellular Plasticity linked with Repeat Element Dysregulation

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are preinvasive pancreatic lesions with a spectrum of histologic phenotypes and variable risk in progressing to invasive cancer. Aberrant repetitive element expression has been shown to be functionally linked to cell state changes in pancreatic cancer. ObjectiveThis study utilized spatial transcriptomics with customized repeat element probes to better understand the relationship of histologic subtypes, repeat element dysregulation, and molecular profiles of different cell populations in IPMN. DesignA total of 52 lesions from 18 patients with resected IPMNs of different histologies and degrees of dysplasia were analyzed with whole transcriptome spatial analysis (GeoMx). Of these, 50 lesions from 17 patients were also processed for single-cell spatial molecular imaging (CosMx). Repeat element probes for LINE1, HSATII, HERVK, and HERVH were used for GeoMx and CosMx. ResultsPancreaticobiliary-type IPMN was enriched for basal-like epithelium and infiltration of Treg cells. Intestinal-type IPMN was enriched for classical epithelium and macrophage infiltrates. Gastric-type IPMN was found to have equal basal-like and classical epithelium with a diverse immune infiltrate. Repeat RNAs were expressed at high levels across IPMN phenotypes and enriched in high-grade dysplasia. Single-cell transcriptional trajectory analysis revealed a phylogeny starting from gastric toward intestinal and pancreaticobiliary branches associated with higher-grade dysplasia and repeat RNA expression. ConclusionSpatial transcriptomics of IPMN identified a molecular continuum between histological subtypes supporting a common gastric-type origin that transitions to intestinal and pancreatobiliary phenotypes. This cell state plasticity is linked with repeat element expression that can be a potential biomarker for IPMN progression. What is already known on this topicO_LIMolecular characterization of IPMN subtypes using regional spatial transcriptomics has described the differences between histologies C_LIO_LIRepeat element expression is associated with cell state changes in pancreatic ductal neoplasm C_LI What this study addsO_LISingle cell spatial molecular imaging of IPMN subtypes reveals a cellular and molecular continuum starting from gastric histology with distinct branches to Intestinal and pancreatobiliary subtypes C_LIO_LIRepeat element expression is associated with higher grade IPMN histology C_LIO_LIRepeat element expression is elevated in the histologic and molecular continuum from gastric to intestinal and pancreatobiliary-type IPMN C_LI How this study might affect research, practice, or policyO_LIThese results support a common gastric histology origin of IPMN subtypes with different molecular trajectories towards higher grade disease C_LIO_LIOur findings suggest that repeat RNA expression can be used in conjunction with other transcriptional markers of cell state as a biomarker for IPMN progression C_LI

cancer biology↗

bioRxiv2025

An Enhanced Conditional Variational Autoencoder-Based Normative Model for Neuroimaging Analysis

Normative modelling in neuroimaging provides a powerful framework for quantifying individual deviations from expected brain measures as a function of relevant covariates. While most established approaches have focused on analysing distinct variables in isolation, there is a growing need for deep learning-based methods capable of handling multiple response variables simultaneously. Conditional variational autoencoders (cVAEs) have previously been applied in this context; however, existing inference methods still face challenges in providing reliable probabilistic predictions. In this study, we introduce an enhanced cVAE-based framework for normative modelling of neuroimaging data. Our key contribution is the development of a novel inference method that integrates latent space sampling and bootstrapping. This method directly leverages the generative nature of cVAEs to estimate the conditional distributions of brain measures. We demonstrate the effectiveness of this approach using white matter hyperintensity (WMH) volumes as a test case for developing, testing, and validating the model. Our dataset includes 8,551 normotensive and 18,180 hypertensive participants from the UK Biobank. We evaluated our method against three well-established and popular normative modelling techniques, including Generalised Additive Models for Location, Scale, and Shape (GAMLSS), Multivariate Fractional Polynomial Regression (MFPR), and Hierarchical Bayesian Regression (HBR). Our results indicate that the proposed cVAE-based framework achieves comparable performance across various metrics, while capturing individual deviations that correlate with the severity of hypertension. The model is particularly well-suited for high-dimensional, non-linear data, making it a robust tool for assessing individual deviations in brain structure. This enhanced normative modelling architecture paves the way for more nuanced and reliable assessments of brain health, with potential implications for personalised medicine and early detection of neurological disorders.

neuroscience↗

bioRxiv2025

Transplant immunosuppressant therapies induce unique functional changes in lymph node and re-shape gut immune homeostasis

BackgroundLifelong immunosuppressive therapy is required to prevent allograft rejection in organ transplantation. Current immunosuppressants effectively suppress adaptive and innate immune responses, but their broad, antigen-non-specific effects often result in severe off-target complications. It remains a significant unmet medical need in transplant medicine. ResultsIn this study we investigated immunosuppressant effects of four major immunosuppressant classes, including tacrolimus, prednisone, mycophenolate mofetil (MMF), and fingolimod (FTY), on the gut microbiome, metabolic pathways, lymphoid architecture and lymphocyte trafficking after up to 30-day chronic exposure. Despite their distinct mechanisms of action and not designed to target the gut, all immunosuppressive drugs induced profound and time-dependent alterations in both intestine gene expression and gut microbiome composition. Progressive alterations from moderate early, drug-specific changes to a strikingly convergent microbial dysbiosis, marked by significant expansion of pathobionts of Muribaculaceae, occurred across all drug classes. Concurrently, all drugs uniformly induced significant suppression of mucosal immunity including B cell, immunoglobulin, and antigen recognition. Time-dependent changes in lymph node (LN) reorganization and cellular composition were also observed, marked by a progressive shift toward pro-inflammatory phenotypes in gut-draining mesenteric LNs and a gradual loss of tolerogenic architecture in peripheral LNs. Drug-specific metabolic alterations and distinct phases of intestinal transcriptional responses were also characterized. Notably, MMF and FTY demonstrated the most robust immunomodulatory properties, and were able to suppress alloantigen-induced inflammation through mediating regulatory T cell distribution and LN remodeling. ConclusionsTogether, these findings highlight the underappreciated complexity and temporal dynamics immunosuppressants effects, particularly their impact on the gut and compartmentalized regulation of alloimmune in lymphoid tissues. Understanding these relationships offers new opportunities for refining immunosuppressive strategies to reduce treatment-related off-target complications and improve long-term organ transplant outcomes.

immunology↗

bioRxiv2025

Neural circuits between nodose ganglion and pulmonary neuroendocrine cells regulate lung inflammatory responses

The lungs are organs exposed to the external environment, and the air we inhale contains various pathogens, such as endotoxins. The vagus nerve, which innervates the lungs, may play a role in detecting pathogens that invade the lungs. Through transcriptome analysis, tissue clearance imaging, electrical excitability recording, and gene- and cell-specific knockout experiments, we found that vagus nerve endings innervate pulmonary neuroendocrine cells (PNECs). These nerve endings sense bacterial endotoxins via pain receptors (TRPA1) rather than toll-like receptors (TLR4), eliciting electrical excitation and enhancing the production of neuropeptides (CGRP) in the nodose ganglia. In turn, CGRP released by sensory neurons from the nodose ganglia promotes both neuropeptide production and the proliferation of PNECs, thereby amplifying endotoxin-induced lung inflammatory responses. This reveals that the neural circuits between the nodose ganglion and PNECs play a critical role in regulating lung inflammatory responses.

neuroscience↗

bioRxiv2024

Atypical Visual Selective Attention in Children with Dyslexia: Evidence from N2pc and PD

Efficient visual attention is fundamental to the development of reading abilities. Previous studies have identified visual attention impairments in individuals with dyslexia, particularly in visual attention span and sluggish attention shifting. However, findings regarding basic visual selective attention remain controversial. To address this issue, the present study provides event-related potential (ERP) evidence to verify whether children with developmental dyslexia (DD) suffered from deficits in visual selective attention. A pop-out visual search task was used to examine visual attentional patterns to a lateral target in 66 children (33 children with DD and 33 typically developing (TD) children) using electroencephalography. Compared to TD children, children with DD showed a larger and prolonged P1 component, as well as a larger target-evoked N2pc component. The larger P1 amplitude was associated with lower reading fluency while the larger N2pc amplitude was associated with poor reading comprehension performance. Interestingly, the target-elicited N2pc was followed by positivity (PD component) in TD children but not in children with DD; however, the N2pc amplitude was correlated with the PD amplitude in children with DD. Children with DD show immature early attentional processing and may have an imbalance in the regulation of visual selective attention between attentional selection and suppression. Our findings provide ERP evidence for interpreting the underlying neural mechanism of visual selective attention in children with DD and may offer a new perspective for exploring the mechanism of visual attention deficits in dyslexia. Research HighlightsO_LIIn a pop-out visual search task, children with dyslexia exhibited a larger N2pc and an absent PD component. C_LIO_LIThe absence of the PD component in children with dyslexia may be associated with their larger N2pc amplitudes. C_LIO_LIN2pc amplitude is associated with reading ability in children with dyslexia. C_LIO_LIChildren with dyslexia need to allocate more resources towards the target but also struggle to disengage from the attended location. C_LI

neuroscience↗

bioRxiv2024

Dynamic p21-dependency during quiescence arrest unveiled by a rapid p21 depletion system

Stress- or developmentally-induced signals can trigger G0/G1 cell cycle arrest through the upregulation of p21, a key inhibitor that halts proliferation. While p21 is widely recognized as essential for establishing this arrest, its degradation is generally assumed to be a prerequisite for the exit from arrest and cell cycle re-entry. Using a rapid p21 degradation system that allows for both endogenous p21 tracking and controlled depletion, we uncovered an extended role for p21 during the exit from G0/G1 arrest. Our results showed that removal of the arrest inducing signals did not lead to an immediate decline of p21 during the exit process; instead, p21 levels continued to maintain for a period before its gradual down-regulation. Importantly, premature depletion of p21 during this process weakened the capacity of cell cycle re-entry, particularly in cells with high levels of pre-existent p21. We found that during the release from arrest, cells with high levels of pre-existent p21 but a premature p21 depletion exhibited reduced capacity to restore KRAS/ERK activity, and supplementing KRAS/ERK activity rescued the failure of cell cycle re-entry in these cells. These findings reveal a previously unappreciated function for p21 during the exit from G0/G1 arrest, aside and distinct from its role in initiating the arrest. This new paradigm extends across multiple cell lines and stress-induced arrest contexts, offering a new framework for understanding p21 function in response to anticancer therapies and in development.

cell biology↗

bioRxiv2024

Targeting and anchoring the mechanosensitive ion channel Piezo to facilitate its inhibition of axon regeneration

Mechanical force orchestrates a myriad of cellular events including inhibition of axon regeneration, by locally activating the mechanosensitive ion channel Piezo enriched at the injured axon tip. However, the cellular mechanics underlying Piezo localization and function remains poorly characterized. We show that the RNA repair/splicing enzyme Rtca acts upstream of Piezo to modulate its expression and transport/targeting to the plasma membrane via Rab10 GTPase, whose expression also relies on Rtca. Loss or gain of function of Rab10 promotes or impedes Drosophila sensory neuron axon regeneration, respectively. Rab10 mediates the cell surface expression of integrin {beta}1 (Itgb1)/mys, which colocalizes and genetically interacts with Piezo, facilitating its anchorage and engagement with the microenvironment, and subsequent activation of mechanotransduction to inhibit regeneration. Importantly, loss of Rtca, Rab10 or Itgb1 promotes CNS axon regeneration after spinal cord injury or optic nerve crush in adult mice, indicating the evolutionary conservation of the machinery.

neuroscience↗

bioRxiv2024

Exploring Genetic Interactions with Rare Variants Reveals Gene Networks Susceptible to Complex Diseases

Genetic interactions play a crucial role in understanding the susceptibility and etiology of complex human diseases. However, existing methods for analyzing gene-gene interactions are often limited to common variants and may not capture the effects of rare variants. In this study, we propose a novel method called GGI-RUNNER that is specifically designed for analyzing gene-gene interactions of rare variants. GGI-RUNNER evaluates the enrichment of rare variant interaction burden in patients relative to baselines in the general population. The baselines are estimated for pairwise genes by a recursive truncated negative-binomial regression model on multiple genomic features available from public data. Intensive simulations demonstrate that GGI-RUNNER exhibits substantially higher statistical power than alternative epistasis tests and maintains reasonable type I error rates even in stratified populations. Applied to real data, GGI-RUNNER identified significant rare variant interactions associated with Alzheimers disease, Hirschsprungs disease, Ulcerative colitis and Crohns disease. Furthermore, we found that these identified genes for each trait can form interconnected networks, which may provide valuable insights into the underlying molecular mechanisms.

bioinformatics↗

bioRxiv2024

Flexibility in Gene Coexpression at Developmental and Evolutionary Timescales

The explosion of next-generation sequencing technologies has allowed researchers to move from studying single genes to thousands of genes, and thereby to also consider the relationships within gene networks. Like others, we are interested in understanding how developmental and evolutionary forces shape the expression of individual genes, as well as the interactions among genes. In pursuing these questions, we confronted the central challenge that standard approaches fail to control the Type I error and/or have low power in the presence of high dimensionality (i.e., large number of genes) and small sample size, as in many gene expression studies. To overcome these challenges, we used random projection tests and correlation network comparisons to characterize differences in network connectivity and density. We detail central challenges, discuss sample size guidelines, and provide rigorous statistical approaches for exploring coexpression differences with small sample sizes. We apply these approaches in a species known for rapid adaptation - the Trinidadian guppy (Poecilia reticulata). Our findings provide evidence for coexpression network differences at developmental and evolutionary timescales and suggest that flexibility in gene coexpression relationships could promote evolvability.

evolutionary biology↗

bioRxiv2024

Expanding GABAergic Neuronal Diversity in iPSC-Derived Disease Models

GABAergic interneurons comprise diverse molecular and functional subtypes that contribute to neural circuit assembly and are implicated in a range of neurodevelopmental and neuropsychiatric disorders. Traditional approaches for differentiating human pluripotent stem cells (PSCs) into neurons often face challenges such as incomplete neural differentiation, prolonged culture periods, and variability across PSC lines, which can constrain their application in disease modeling. To address these limitations, we developed a strategy that combines inducible expression of the transcription factors (TFs) ASCL1 and DLX2 with dual-SMAD and WNT inhibition to efficiently drive differentiation of human PSCs into diverse, region-specific GABAergic neuronal types. Using single-cell sequencing, we characterized the cellular heterogeneity of GABAergic induced neurons (iNs) generated with the patterning factors (patterned iNs) and those derived solely with TFs (PSC-derived iNs), revealing distinct interneuron subtype compositions and the regulatory programs that govern their fate specification. Patterned iNs exhibited gene expression features corresponding to multiple brain regions, particularly the ganglionic eminence (GE) and neocortex, whereas GABAergic PSC-derived iNs predominantly resembled hypothalamic and thalamic neurons. Both iN types were enriched for genes relevant to neurodevelopmental and psychiatric disorders, with patterned iNs more specifically linked to neural lineage genes, highlighting their utility for disease modeling. We further applied this protocol to investigate the impact of a recurrent ADNP syndrome-associated mutation (p.Tyr719*) on GABAergic neuron differentiation, revealing that this mutation disrupts GABAergic fate specification and synaptic transmission. Overall, this study expands the toolkit for disease modeling by demonstrating the complementary advantages of GABAergic PSC-derived iNs and patterned iNs in representing distinct GABAergic neuron subtypes, brain regions, and disease contexts. Together, these approaches provide a flexible platform for investigating molecular and cellular mechanisms relevant to neurodevelopmental and neuropsychiatric disorders.

developmental biology↗

bioRxiv2024

Optimizing femtosecond laser fabricating strategy of Nitinol hypotube for vascular interventional surgery

Guidewires and catheters are essential in minimally invasive procedures, particularly in accessing targets within the vascular system for neuron surgery. Femtosecond lasers can precisely cut nickel-titanium micro tubes, known as Nitinol hypotubes, serving as the heads of micro guidewires while protecting their core tips. The quality and geometry of these hypotubes depend on the focus of the laser cutting system. We evaluated the cutting efficiency and quality of Nitinol hypotubes using objective lenses with three numerical apertures (NA). Quantitative analysis indicated that higher NA objectives yield better surface quality, resulting in lower debris. Additionally, cutting with high NA objectives produced significantly lower arithmetic mean surface roughness and enhanced mechanical properties. Using a two-temperature model, we simulated the interaction between femtosecond lasers and Nitinol, showing that higher NA objectives increase electron temperatures, thus improving material removal efficiency. This study also tested the optimized Nitinol hypotube prformance in simulations of invasive neuron surgery.

neuroscience↗

bioRxiv2024

Large-scale Signal Propagation Modes in the Human Brain

The brains large-scale temporal dynamics play a crucial role in understanding its operations, but developing a cohesive framework to integrate the potentially extensive array of spatiotemporal patterns remains elusive. Our work addresses this gap by identifying multiple large-scale signal propagation modes in resting-state fMRI time series under a unified methodological framework. We found five distinct modes that effectively predict future blood-oxygen-level-dependent (BOLD) signal dynamics, each reconciling transitions between well-known large-scale brain networks into coherent spatiotemporal units. By utilizing these coherent units, our approach circumvents the need to explore combinatorial explosion of transitions between potential states, enabling parsimonious modeling and effective prediction of whole-brain temporal evolution. Each mode captures specific operational dimensions of neural resource allocation, ensuring their interpretability. Importantly, we showed that complex spatiotemporal features emerge from the superposition of these few propagation modes, unifying a broad spectrum of well-known brain dynamics phenomena. Our results lay the groundwork for a unified framework to understand large-scale spatiotemporal brain organization. Moreover, individual differences in mode expression profiles correlate with general cognitive abilities, exhibit heritability, and demonstrate cross-task stability, underscoring their functional significance. This could lead to efficient methods for characterizing functional fingerprints and advancing diagnostic approaches for neurological disorders.

neuroscience↗

bioRxiv2024

Undergraduate research project uncovers a novel strain of amphibian chytrid fungus in the Northeastern United States

Investigation of the genetic variation of Batrachochytrium dendrobatidis (Bd or chytrid fungus) in New Hampshire (NH) in the northeastern U.S. has shown the presence of genetic mutations which are currently undocumented in the literature. DNA was collected as part of a long-term monitoring project in New Hampshire to test for the presence of Bd in amphibian populations. In this monitoring project, we are detecting the presence of Bd in multiple populations, but the observed amphibians do not appear to have increased mortality or other symptoms related to the fungus. To further investigate the strain of Bd affecting NH amphibians, we sequenced samples that were collected in 2019, as part of your yearly monitoring effort. Utilizing the Basic Local Alignment Search Tool (BLAST) and sequences available on GenBank, we found that there are two different strains of chytrid in the observed NH amphibians. These strains are similar to strains noted previously in New England, but exhibit unique point mutations and in one case, a deletion. These variations could affect the impact that Bd has on amphibians in this region, and therefore could contribute to a better understanding of the variation in strains of chytrid and how they impact amphibian populations around the world. This study highlights the importance of monitoring efforts conducted at smaller, non-research institutions and we encourage other small institutions to take up similar monitoring efforts for Bd or other national or global conservation concerns.

ecology↗

bioRxiv2024

Mechanical coupling between dorsal and ventral surfaces shapes the Drosophila haltere

The extracellular matrix is an essential determinant of animal form, enabling organization of cells and tissues into organs with complex 3D shapes. In contrast with the dorso-ventrally flat Drosophila wing, its serial homolog the haltere adopts a globular shape thought to arise from a lack of matrix-mediated adhesion between its dorsal and ventral surfaces. Contradicting this model, however, matrix manipulations are known to deform halteres. To understand haltere morphogenesis, we characterized matrix behavior and monitored metamorphic development of the haltere. We found that, similar to the wing, correct haltere morphogenesis requires Collagen IV degradation, which we show is mediated by ecdysone-controlled expression of Matrix metalloprotease 2 in both wing and haltere. After Collagen IV is degraded, similar again to the wing, dorsal and ventral haltere surfaces establish Laminin-mediated contact through long cytoskeletal projections. Furthermore, time-lapse analysis of shape changes in wild type and mutant halteres indicates that these projections couple the two surfaces through a central tensor, ensuring load distribution across the whole organ to create a globular shape against tissue-wide deforming forces. Our findings reveal an unexpected role for matrix-mediated adhesion in haltere morphogenesis and describe a novel type of matrix-based tensor structure building 3D shape from 2D epithelia.

developmental biology↗

bioRxiv2024

Ecological synchrony in human-modified landscapes under a changing climate

Different aspects of ecological systems, biotic or abiotic, often fluctuate in coordinated patterns over space and time. Such high concordance between ecological processes is often referred to as ecological synchrony. Anthropogenic activities, including and beyond climate change, have the potential to alter ecological synchrony by disrupting or enhancing existing synchrony. Despite many local studies, we have a limited systematic understanding of how ecological synchrony is shaped by management in human-dominated landscapes at regional to continental scales. From a macrosystems perspective, we review how anthropogenic activities, particularly beyond climate change, alter ecological synchrony across levels of ecological organization, from the ecosystem level to the population level. For each level, we use a large-scale case study to demonstrate ways to quantify the impacts of human modifications on synchrony using big data from remote sensing, surveys, and observatory networks. For example, we detected possible homogenization of population dynamics of bird species in North America. These changes in ecological synchrony, although in different forms, often represent challenges to ecological and social systems. Collaborative research efforts that integrate emerging open data streams moving forward will be able to provide insights into the effects of different anthropogenic drivers and the consequences of changes in synchrony.

ecology↗

bioRxiv2024

Vinculin Y822 phosphorylation regulates cardiomyocyte adhesion dynamics and adherens junction maturation in the heart

In the heart, cell-matrix and cell-cell adhesions reorganize in response to increased cardiac demand and growth to promote cardiomyocyte maturation. Vinculin, a mechanosensitive adaptor protein, links filamentous actin to cell-matrix and cell-cell adhesions and is thus positioned to regulate adhesion reorganization. However, how the two adhesion systems are coordinated in the heart, and the role of vinculin in this process is poorly understood. Here, we define the role of vinculin phosphorylation at tyrosine residue 822 (pY822) in cardiomyocyte adhesion and heart function. We found that pY822 correlated with dynamic junction remodeling in the developing heart but was lost as junctions matured postnatally. We then mutated Y822 to phenylalanine (Y822F) in the mouse to determine pY822 function in vivo. Homozygous mutant Vcl Y822F mice were viable and exhibited normal cardiac function at ten weeks of age; however, cardiac dysfunction was observed at 28 weeks. Vinculin and adherens junction proteins were reduced at cardiomyocyte junctions in Y822F hearts. In contrast, 5/{beta}1 integrin and fibronectin increased along the lateral border of Y822F cardiomyocytes. Our results demonstrate that vinculin Y822 phosphorylation regulates the balance between cadherin and integrin adhesion organization, highlighting the importance of post-translational modification in modulating vinculin function in heart physiology.

cell biology↗