Biology subjects

Inoue, T.

Publications and source records attributed to Inoue, T..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Light-guided actin polymerization drives directed motility in protocells

Motility is a hallmark of lifes dynamic processes, enabling cells to actively chase prey, repair wounds, and shape organs. Recreating these intricate behaviors using well-defined molecules remains a major challenge at the intersection of biology, physics, and molecular engineering. Although the polymerization force of the actin cytoskeleton is characterized as a primary driver of cell motility, building a minimal platform to test this process in protocellular systems has proven elusive. The difficulty lies in the daunting task of distilling key components from motile cells and integrating them into model membranes in a physiologically relevant manner. To address this, we developed a method to optically control actin polymerization with high spatiotemporal precision within cell-mimetic lipid vesicles known as giant unilamellar vesicles (GUVs). Within these active protocells, the reorganization of actin networks triggered outward membrane extensions as well as the unidirectional movement of GUVs at speeds of up to 0.43 {micro}m/min, within the range of adherent mammalian cells. Notably, our findings reveal the requirements of both branched and linear actin networks for efficient membrane protrusions. This approach offers a powerful platform for unraveling the intricacies of cell migration, designing synthetic cells with active morphodynamics, and advancing bioengineering applications, such as self-propelled delivery systems and autonomous tissue-like materials.

synthetic biology↗

bioRxiv2024

The lysosomal membrane protein LAMP2B mediates microlipophagy to target obesity-related disorders

Lifestyle diseases, such as obesity, diabetes, and metabolic syndrome, are leading health problems, most of which are related to abnormal lipid metabolism. Lysosomes can degrade lipid droplets (LDs) via microautophagy. Here, we report the molecular mechanism and pathophysiological roles of microlipophagy, regulated by the lysosomal membrane protein LAMP2B. Our study revealed that LAMP2B interacts with phosphatidic acid, facilitating lysosomal-LD interactions and enhancing lipid hydrolysis via microlipophagy depending on endosomal sorting complexes required for transport. Correlative light and electron microscopy demonstrated direct LDs uptake into lysosomes at contact sites. Moreover, LAMP2B overexpression in mice prevents high-fat diet-induced obesity, insulin resistance, and adipose tissue inflammation; liver lipidomics analysis suggested enhanced triacylglycerol hydrolysis. Overall, the findings of this study elucidated the mechanism of microlipophagy, which could be promising for the treatment of obesity and related disorders.

cell biology↗

bioRxiv2024

3D Reconstruction of Neuronal Allometry and Neuromuscular Projections in Asexual Planarians Using Expansion Tiling Light Sheet Microscopy

The intricate coordination of the neural network in planarian growth and regeneration has remained largely unrevealed, partly due to the challenges of imaging the central nervous system (CNS) in three dimensions (3D) with high resolution and within a reasonable timeframe. To address this gap in systematic imaging of the CNS in planarians, we adopted high-resolution, nanoscale imaging by combining tissue expansion and tiling light-sheet microscopy, achieving up to 4-fold linear expansion. Using an automatic 3D cell segmentation pipeline, we quantitatively profiled neurons and muscle fibers at the single-cell level in over 400 wild-type planarians during homeostasis and regeneration. We validated previous observations of neuronal cell number changes and muscle fiber distribution. We found that the increase in neuron cell number tends to lag behind the rapid expansion of somatic cells during the later phase of homeostasis. By imaging the planarian with up to 120 nm resolution, we also observed distinct muscle distribution patterns at the anterior and posterior poles. Furthermore, we investigated the effects of {beta}-catenin RNAi on muscle fiber distribution at the posterior pole, consistent with changes in anterior-posterior polarity. The glial cells were observed to be close in contact with dorsal-ventral muscle fibers. Finally, we observed disruptions in neural-muscular networks in inr-1 RNAi planarians. These findings provide insights into the detailed structure and potential functions of the neural-muscular system in planarians and highlight the accessibility of our imaging tool in unraveling the biological functions underlying their diverse phenotypes and behaviors.

developmental biology↗

bioRxiv2024

Long-lasting negative effects of past forestation on grassland pollination networks and their function

O_LIGrasslands are facing a rapid decline worldwide. Among the primary threats to these ecosystems are changes in land use, such as land abandonment and forestation, which promote forest vegetation in detriment of grassland plant diversity. To support the conservation and restoration of grasslands, it is key to understand what ecological processes limit the recovery of their biodiversity and functions after perturbations. However, we still know little about the legacy effects of forestation on the ecological mechanisms involved in the recovery of grasslands, especially concerning long-lasting impacts on plant-pollinator interaction networks and plant reproduction. C_LIO_LIHere, we aim to fill this gap of knowledge by comparing the plant and pollinator diversity, the degree of network generalization, the pollination success and pollen limitation of native plant species in 30 plant-pollinator networks of old-growth and restored grasslands of different ages since recovery (from 2 to 84 years). We hypothesized that past forestation would exert long-lasting legacy negative effects on plant richness and plant-pollinator networks, increasing pollen limitation for native plants, thereby delaying community recovery in restored grasslands. C_LIO_LIResults showed that restored grasslands exhibited significantly lower plant richness, less specialized (more generalized) interaction networks, lower pollination success and pollen-limited seed reproduction of native plants compared to old-growth grasslands. Meanwhile, the degree of network specialization and pollination success gradually increased with time after grassland restoration initiated. Overall, network generalization, which was caused by low plant richness, reduced pollination and reproduction success in native grassland plants, and degraded pollination networks and functions could recover in restored grasslands with continuous management. These findings imply that plant diversity restoration was slow because of the negative feedbacks associated with low plant richness and consequently, generalized plant-pollinator interaction networks, which diminished native plant reproduction in restored grasslands. C_LIO_LISynthesis and applications Our findings suggest that the recovery of specialized plant-pollinator networks by enhancing plant diversity is essential for restoring pollination function. For quicker grassland restoration, it may be effective to facilitate the establishment of highly specialized pollination networks by seeding or planting diverse native plants collected from neighbouring areas while avoiding genetic contamination. C_LI

ecology↗

bioRxiv2024

Vasopressin-to-Oxytocin Receptor Crosstalk in the Preoptic Area Underlying Parental Behaviors in Male Mice

The transition to parenthood brings significant changes in behavior toward offspring. For instance, in anticipation of their offspring, male mice shift from infanticidal to caregiving behaviors. While the release of oxytocin from the paraventricular hypothalamus (PVH) plays a critical role in paternal caregiving, it does not fully account for the entire behavioral shift. The specific downstream neurons and signaling mechanisms involved in this process remain obscure. Here, we demonstrate that PVH vasopressin neurons also essentially contribute to a paternal behavioral shift. This vasopressin signal is partially transmitted through oxytocin receptors (OTRs) expressed in the anterior commissure and medial nuclei of the preoptic area. These OTR-expressing neurons receive inputs from both PVH oxytocin and vasopressin neurons and are responsible for expressing paternal caregiving behaviors. Collectively, this non-canonical vasopressin-to-OTR crosstalk within specific limbic circuits acts as a pivotal regulator of paternal behavioral changes in mice. HighlightsO_LIPVH vasopressin neurons are required for and can trigger paternal caregiving behaviors. C_LIO_LIVasopressin-induced paternal behaviors are mediated in part by OTRs in the preoptic area (POA). C_LIO_LIPOA OTR neurons receive inputs from both PVH oxytocin and vasopressin neurons. C_LIO_LIPOA OTR neurons play a critical and facilitative role in promoting paternal caregiving behaviors. C_LI

neuroscience↗

bioRxiv2024

The yolk sac vasculature in early avian embryo provides a novel model for the analysis of cancer extravasation

Hematogenous metastasis, a key trait of cancer cells, involves a complex sequence of cell migration steps, including intravasation, circulation, arrest in capillary vessels, and extravasation. Among these steps, extravasation is challenging to image in amniotes like humans and mice due to its unpredictable timing and location, limiting our understanding of cellular and molecular mechanisms through imaging. Establishing a new cancer carrier model with high-resolution imaging capabilities in amniotes is crucial. In this study, we investigated the yolk sac vasculature (YSV) of early avian embryos (chickens and quail) as a new model for studying extravasation, offering excellent imaging capabilities. We examined the YSV structure and attempted fluorescent labeling to enhance visibility. We then injected mCherry-labeled HT-1080 cells into YSV and observed their behavior, revealing distinct morphologies and extravasation dynamics. Our findings suggest that the YSV model holds promise as a novel cancer carrier model for elucidating cellular and molecular mechanisms through imaging-based approaches.

cancer biology↗

bioRxiv2024

Development of a noninvasive olfactory stimulation fMRI system in marmosets

Olfactory dysfunction is associated with aging and the earliest stages of neurodegenerative diseases, such as Alzheimers and Parkinsons diseases; it is thought to be an early biomarker of cognitive decline. In marmosets, a small non-human primate model used in brain research, olfactory pathway activity during olfactory stimulation has not been well studied because of the difficulty in clearly switching olfactory stimuli inside a narrow MRI. Here, we developed an olfactory-stimulated fMRI system using a small-aperture MRI machine. The olfactory presentation system consisted of two tubes, one for supply and one for suction of olfactory stimulants and a balloon valve. A balloon valve installed in the air supply tube controlled the presentation of the olfactory stimulant, which enabled sharp olfactory stimulation within MRI, such as 30 seconds of stimulation repeated five times at five-minute intervals. The olfactory stimulation system was validated in vivo and in a simulated system. fMRI analysis showed a rapid increase in signal values within 30 s of olfactory stimulation in eight regions related to the sense of smell. As these regions include those associated with Alzheimers and Parkinsons diseases, olfactory stimulation fMRI may be useful in clarifying the relationship between olfactory dysfunction and dementia in non-human primates.

physiology↗

bioRxiv2024

AUTS2, a causative gene for microcephaly, regulates division of intermediate progenitor cells and production of upper-layer neurons

AUTS2 mutations often exhibit neurodevelopmental disorders and microcephaly. However, how AUTS2 regulates neuron production and affects brain size remains unclear. Here, we show that AUTS2 cooperates with the Polycomb complex PRC2 to regulate gene expression and cortical neurogenesis. Auts2 mutant mice exhibit reduced division of intermediate progenitor cells (IPCs), leading to decreased neurons and thickness in the upper-layer cortex. Expression of Robo1 is increased in the mutants, which in turn suppresses IPC division. Transcriptome and chromatin profiling experiments show that, in IPCs, AUTS2 primarily represses transcription of genes, including Robo1. Promoter region of AUTS2 target genes is enriched with H3K27me3, a repressive histone modification, but its levels are reduced in Auts2 mutants. AUTS2 interacts with PRC2, and together, they promote IPC division. These suggest that AUTS2 collaborates with PRC2 to repress gene transcription through H3K27 trimethylation, promoting neuron production. This sheds light on AUTS2 pathophysiological mechanisms in neurogenesis and microcephaly.

neuroscience↗

bioRxiv2024

Parallel Labeled-Line Organization of Sympathetic Outflow for Selective Organ Regulation in Mice

The sympathetic nervous system is vital in maintaining homeostasis and responding to environmental changes1-3. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), which influence various organs both through neuronal pathways via postganglionic neurons and through endocrine processes by innervating the adrenal gland. Despite decades of research supporting the concept of selective control within this system1,4-9, the neural circuit organization responsible for the specificity of sympathetic outflow remains poorly understood. Notably, classical anatomical studies in rats have not revealed a definitive molecular code governing SPNs, nor have they confirmed the existence of SPNs strictly corresponding to specific output targets1,6,10,11. To reconcile this discrepancy, we aim to integrate recent transcriptome data of SPNs12,13 in mice with viral-genetic toolkits14 to map axonal projections and manipulate the functions of SPNs governing the gastrointestinal tract and adrenal gland. Here, we have identified two subtypes of SPNs in the lower thoracic spinal cord, defined at the molecular level, exhibiting non-overlapping patterns of innervation. Chemogenetic manipulations on these distinct SPN subtypes revealed selective impacts on the digestive functions in the gastrointestinal tracts or glucose metabolism mediated by the adrenal gland, respectively. This molecularly delineated parallel labeled-line organization in sympathetic outflows presents a potential avenue for selectively manipulating organ functions.

neuroscience↗

bioRxiv2024

A fatal case of peritonitis caused by Dysgonomonas capnocytophagoides harboring the novel metallo-beta-lactamase gene blaDYB-1

Dysgonomonas capnocytophagoides shows multidrug resistance to antibiotics and causes opportunistic infections in immunocompromised hosts. We report a fatal case of peritonitis caused by D. capnocytophagoides in Japan. We identified a novel chromosomally encoded class B1 metallo-beta-lactamase gene designated blaDYB-1 and an ermFS gene that contributed to multidrug resistance.

microbiology↗

bioRxiv2023

Development of a non-invasive novel individual marmoset holder for evaluation by awake functional magnetic resonance brain imaging

BackgroundAlthough functional MRI (fMRI) in awake marmosets (Callithrix jacchus) is fascinating for functional brain mapping and evaluation of brain disease models, it is difficult to launch awake fMRI on scanners with less than 15 cm of bore size. A universal marmoset holder for the small-bore size MRI was designed, and evaluated whether this holder could conduct auditory stimulation fMRI in the awake state. New MethodThe marmoset holder was designed with an outer diameter of 71.9 mm. A holder was designed to allow adjustment according to the individual head shape, enabling to use the holder universally. An awake fMRI study of auditory response was conducted to evaluate the practicality of the new holder. Whole-brain activation was investigated when marmosets heard the marmoset social communication "phee call," an artificial tone sound, music (bossa nova), and reversed of those. ResultsThe prefrontal cortex was significantly activated in response to phee calls, whereas only the auditory cortex was activated in response to pure tones. In response to bossa nova, the marmosets visual and auditory cortices were activated. In contrast, the auditory response was decreased when marmosets heard phee calls and bossa nova music played backward. Their stimulus-specific responses indicated they perceived and differentiated sound characteristics in the fMRI environment. Comparison with Existing MethodsA holder does not require surgical intervention or custom-made helmet to minimize head movement in small space. ConclusionOur newly developed holder made it possible to perform longitudinal fMRI experiments on multiple marmosets in a less invasive manner. HighlightO_LIWe designed a universal marmoset holder for the optimization of small-bore size MRI. We aimed to evaluate whether the data acquired by fMRI with this holder indicated that awake marmosets were likely to recognize sounds during fMRI and whether the brain activity shown as fMRI signals reflected the characteristics of each sound. C_LIO_LIAfter the acclimatization of the marmosets to the holder, an awake fMRI study was conducted to evaluate the practicality of the new holder and successfully acquired the auditory responses to the set of sound stimuli. C_LIO_LIOur newly developed holder does not require surgical intervention to minimize head movement, which allows for less invasive fMRI experiments and makes it easier to conduct longitudinal fMRI for multiple marmosets. C_LI

neuroscience↗

bioRxiv2023

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue are bispecific antibodies which combine the targeting abilities of two antibodies with distinct epitopes. We engineered neutralizing bispecific antibodies in the IgG-scFv format from two initially non-neutralizing antibodies, CvMab-6 (which binds to the receptor-binding domain [RBD]) and CvMab-62 (targeting a spike protein S2 subunit epitope adjacent to the known anti-S2 antibody epitope). Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.

microbiology↗

bioRxiv2023

Synthetic control of actin polymerization and symmetry breaking in activeprotocells

Non-linear biomolecular interactions on the membranes drive membrane remodeling that underlies fundamental biological processes including chemotaxis, cytokinesis, and endocytosis. The multitude of biomolecules, the redundancy in their interactions, and the importance of spatiotemporal context in membrane organization hampers understanding the physical principles governing membrane mechanics. A minimal, in vitro system that models the functional interactions between molecular signaling and membrane remodeling, while remaining faithful to cellular physiology and geometry is powerful yet remains unachieved. Here, inspired by the biophysical processes underpinning chemotaxis, we reconstituted externally-controlled actin polymerization inside giant unilamellar vesicles, guiding self-organization on the membrane. We show that applying undirected external chemical inputs to this system results in directed actin polymerization and membrane deformation that are uncorrelated with upstream biochemical cues, indicating symmetry breaking. A biophysical model of the dynamics and mechanics of both actin polymerization and membrane shape suggests that inhomogeneous distributions of actin generate membrane shape deformations in a non-linear fashion, a prediction consistent with experimental measurements and subsequent local perturbations. The active protocellular system demonstrates the interplay between actin dynamics and membrane shape in a symmetry breaking context that is relevant to chemotaxis and a suite of other biological processes.

synthetic biology↗

bioRxiv2023

Decoding host-microbiome interactions through co-expression network analysis within the non-human primate intestine

The gut microbiome affects the health status of the host through complex interactions with the hosts intestinal wall. These host-microbiome interactions may spatially vary along the physical and chemical environment of the intestine, but these changes remain unknown. This study investigated these intricate relationships through a gene co-expression network analysis based on dual transcriptome profiling of different intestinal sites--cecum, transverse colon, and rectum-- of the primate common marmoset. We proposed a gene module extraction algorithm based on graph theory to find tightly interacting gene modules of the host and the microbiome from a vast co-expression network. The 27 gene modules identified by this method, which include both host and microbiome genes, not only produced results consistent with previous studies regarding the host-microbiome relationships, but also provided new insights into microbiome genes acting as potential mediators in host-microbiome interplays. Specifically, we discovered associations between the host gene FBP1, a cancer marker, and polysaccharide degradation-related genes (pfkA and fucI) coded by Bacteroides vulgatus, as well as relationships between host B-cell specific genes (CD19, CD22, CD79B, PTPN6) and a tryptophan synthesis gene (trpB) coded by Parabacteroides distasonis. Furthermore, our proposed module extraction algorithm surpassed existing approaches by successfully defining more functionally related gene modules, providing insights for understanding the complex relationship between the host and the microbiome. IMPORTANCEWe unveiled the intricate dynamics of the host-microbiome interactions along the colon by identifying closely interacting gene modules from a vast gene co-expression network, constructed based on simultaneous profiling of both host and microbiome transcriptomes. Our proposed gene module extraction algorithm, designed to interpret inter-species interactions, enabled the identification of functionally related gene modules encompassing both host and microbiome genes, which was challenging with conventional modularity maximization algorithms. Through these identified gene modules, we discerned previously unrecognized bacterial genes that potentially mediate in known relationships between host genes and specific bacterial species. Our findings underscore the spatial variations in host-microbiome interactions along the colon, rather than displaying a uniform pattern throughout the colon.

microbiology↗

bioRxiv2023

ECM degradation in the stump region induced by Fgf during functional joint regeneration in frogs

Previous studies indicated the importance of the reciprocal interactions between residual tissues in the stump and the newly formed blastema for achieving functional joint regeneration after amputation at the joint level in newts. This reciprocal interaction during regeneration was named "reintegration". When this reintegration mechanism was evoked in Xenopus leavis, regeneration of a functional joint was induced in frogs. Interestingly, degradation of extracellular matrix (ECM) in the remaining joint cartilage was observed during regeneration in both newts and frogs. Histological and gene expression analyses suggested that the degradation of Type II collagen in the cartilage of the articular head might be performed by matrix metalloproteases (Mmps) which were transiently expressed after amputation. We found that fibroblast growth factor (Fgf) induced Mmps expression in the cartilage of the articular head. These results support the possibility that the Fgf signal induces ECM degradation in joint tissues via Mmps expression and that the ECM degradation and subsequent bone morphogenetic protein (Bmp) secretion promote cell proliferation, migration, and differentiation of the cells in the blastema to achieve functional joint regeneration.

developmental biology↗

bioRxiv2023

Shared GABA transmission pathology in dopamine agonist- and antagonist-induced dyskinesia

Dyskinesia is involuntary movement caused by long-term medication with dopamine-related agents: the dopamine agonist, L-DOPA, to treat Parkinsons disease (L-DOPA-induced dyskinesia [LID]) or dopamine antagonists to treat schizophrenia (tardive dyskinesia [TD]). However, it remains unknown why distinct types of medications for distinct neuropsychiatric disorders induce similar involuntary movements. Here, we searched for a shared structural footprint using magnetic resonance imaging-based macroscopic screening and super-resolution microscopy-based microscopic identification. We identified the enlarged axon terminals of striatal medium spiny neurons in both LID and TD model mice. The striatal overexpression of vesicular gamma-aminobutyric acid transporter (VGAT) was necessary and sufficient for modeling these structural changes; VGAT levels gated the functional and behavioral alterations in dyskinesia models. Our findings indicate that lowered type 2 dopamine receptor signaling with repetitive dopamine fluctuations is a common cause of VGAT overexpression and late-onset dyskinesia formation, and that reducing dopamine fluctuation rescues dyskinesia pathology via VGAT downregulation. HighlightsO_LIEnhancement of GABAergic transmission is a shared mechanism between LID and TD. C_LIO_LIVGAT levels in MSNs govern the structure and function of MSN presynaptic terminals. C_LIO_LIGain and loss of VGAT function in MSNs exacerbates and ameliorates dyskinesia. C_LIO_LILowered D2 signaling with repetitive DA fluctuations causes VGAT overexpression. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/550763v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@15041b4org.highwire.dtl.DTLVardef@9bf41org.highwire.dtl.DTLVardef@1eb7ee4org.highwire.dtl.DTLVardef@1d7dae8_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

A Rapid Inducible RNA Decay system reveals fast mRNA decay in P-bodies

RNA decay plays a crucial role in regulating mRNA abundance and gene expression. Modulation of RNA degradation is imperative to investigate an RNAs function. However, information regarding where and how RNA decay occurs remains scarce, partially because existing technologies fail to initiate RNA decay with the spatiotemporal precision or transcript specificity required to capture this stochastic and transient process. Here, we devised a general method that employs inducible tethering of regulatory protein factors to target RNAs and modulate their metabolism. Specifically, we established a Rapid Inducible Decay of RNA (RIDR) technology to degrade target mRNA within minutes. The fast and synchronous induction enabled direct visualization of mRNA decay dynamics in cells with spatiotemporal precision previously unattainable. When applying RIDR to endogenous ACTB mRNA, we observed rapid formation and disappearance of RNA granules, which coincided with pre-existing processing bodies (P-bodies). We measured the time-resolved RNA distribution in P-bodies and cytoplasm after induction, and compared different models of P-body function. We determined that mRNAs rapidly decayed in P-bodies upon induction. Additionally, we validated the functional role of P-bodies by knocking down specific a P-body constituent protein and RNA degradation enzyme. This study determined compartmentalized RNA decay kinetics for the first time. Together, RIDR provides a valuable and generalizable tool to study the spatial and temporal RNA metabolism in cells.

molecular biology↗

bioRxiv2023

Visualization of trans homophilic interaction of clustered protocadherin in neurons

Clustered protocadherin (Pcdh) functions as a cell recognition molecule through the homophilic interaction in CNS. However, its interactions have yet not been visualized in neurons. We previously reported Pcdh{gamma}B2-FRET probes to be applicable only for cell lines. Herein, we newly designed Pcdh{gamma}B2-FRET probes by fusing FRET donor and acceptor fluorescent proteins to a single Pcdh{gamma}B2 molecule and succeeded in visualizing Pcdh{gamma}B2 homophilic interaction in cultured hippocampal neurons. The {gamma}B2-FRET probe localized in the soma and neurites, and FRET signals were observed at contact sites between neurites and eliminated by EGTA addition. Live imaging revealed that the FRET-negative {gamma}B2 signals were rapidly moving along neurites and soma, whereas the FRET-positive signals remained in place. We observed that the {gamma}B2 proteins at synapses rarely interact homophilically. The {gamma}B2-FRET probe would allow us to elucidate the function of the homophilic interaction and the cell recognition mechanism. Significance StatementWe visualize the Pcdh homophilic interaction using a novel FRET-based probe, and reveal that the homophilically interacting Pcdh proteins are found at contact sites between the neurites and roots of neurites from the soma, and are stable at a location. Additionally, in neurons, Pcdh proteins are located at synapses but rarely interact homophilically.

neuroscience↗