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https://www.readbyqxmd.com/read/28220838/pan-neurexin-perturbation-results-in-compromised-synapse-stability-and-a-reduction-in-readily-releasable-synaptic-vesicle-pool-size
#1
Dylan P Quinn, Annette Kolar, Michael Wigerius, Rachel N Gomm-Kolisko, Hanine Atwi, James P Fawcett, Stefan R Krueger
Neurexins are a diverse family of cell adhesion molecules that localize to presynaptic specializations of CNS neurons. Heterologous expression of neurexins in non-neuronal cells leads to the recruitment of postsynaptic proteins in contacting dendrites of co-cultured neurons, implicating neurexins in synapse formation. However, isoform-specific knockouts of either all α- or all β-neurexins show defects in synaptic transmission but an unaltered density of glutamatergic synapses, a finding that argues against an essential function of neurexins in synaptogenesis...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#2
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194405/abundance-and-significance-of-neuroligin-1-and-neurexin-ii-in-the-enteric-nervous-system-of-embryonic-rats
#3
Dongming Wang, Jingnian Pan, Guoxin Song, Ni Gao, Yi Zheng, Qiangye Zhang, Aiwu Li
Aim. To investigate the abundance of neuroligin-1 and neurexin II in the enteric nervous system (ENS) of rats on different embryonic days and to explore their potential significance. Methods. The full-thickness colon specimens proximal to the ileocecal junction of rats on embryonic days 16, 18, and 20 and of newborns within 24 hours (E16, E18, E20, and Ep0) were studied, respectively. qRT-PCR was applied for detecting the expressions of neuroligin-1 and neurexin II on mRNA, and western blotting was employed for detecting their further expressions on the whole tissue...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28154949/differential-gene-expression-associated-with-honey-bee-grooming-behavior-in-response-to-varroa-mites
#4
Mollah Md Hamiduzzaman, Berna Emsen, Greg J Hunt, Subhashree Subramanyam, Christie E Williams, Jennifer M Tsuruda, Ernesto Guzman-Novoa
Honey bee (Apis mellifera) grooming behavior is an important mechanism of resistance against the parasitic mite Varroa destructor. This research was conducted to study associations between grooming behavior and the expression of selected immune, neural, detoxification, developmental and health-related genes. Individual bees tested in a laboratory assay for various levels of grooming behavior in response to V. destructor were also analyzed for gene expression. Intense groomers (IG) were most efficient in that they needed significantly less time to start grooming and fewer grooming attempts to successfully remove mites from their bodies than did light groomers (LG)...
February 3, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28154140/carbonic-anhydrase-related-protein-ca10-is-an-evolutionarily-conserved-pan-neurexin-ligand
#5
Fredrik H Sterky, Justin H Trotter, Sung-Jin Lee, Christian V Recktenwald, Xiao Du, Bo Zhou, Peng Zhou, Jochen Schwenk, Bernd Fakler, Thomas C Südhof
Establishment, specification, and validation of synaptic connections are thought to be mediated by interactions between pre- and postsynaptic cell-adhesion molecules. Arguably, the best-characterized transsynaptic interactions are formed by presynaptic neurexins, which bind to diverse postsynaptic ligands. In a proteomic screen of neurexin-1 (Nrxn1) complexes immunoisolated from mouse brain, we identified carbonic anhydrase-related proteins CA10 and CA11, two homologous, secreted glycoproteins of unknown function that are predominantly expressed in brain...
February 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28120489/association-study-between-the-neurexin-1-gene-and-tardive-dyskinesia
#6
Rachel Lanning, Tristram A Lett, Arun K Tiwari, Eva J Brandl, Vincenzo de Luca, Aristotle N Voineskos, Steven G Potkin, Jeffrey A Lieberman, Herbert Y Meltzer, Daniel J Müller, Gary Remington, James L Kennedy, Clement C Zai
OBJECTIVE: Tardive dyskinesia (TD) is a motor side effect that may develop after long-term antipsychotic treatment. Schizophrenia has recently been associated with the Neurexin-1 (NRXN1) gene that codes for a cell adhesion molecule in synaptic communication. METHODS: This study examined five NRXN1 single-nucleotide polymorphisms (SNPs) for possible association with the occurrence and severity of TD in 178 schizophrenia patients of European ancestry. RESULTS: We did not find these SNPs to be significantly associated with TD...
January 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28120348/effects-of-cadmium-manganese-and-lead-on-locomotor-activity-and-neurexin-2a-expression-in-zebrafish
#7
Hongwei Tu, Chengji Fan, Xiaohui Chen, Jiaxian Liu, Bin Wang, Zhibin Huang, Yiyue Zhang, Xiaojing Meng, Fei Zou
The synaptic adhesion protein Neurexin 2a (Nrxn2a) plays a key role in neuronal development and is associated with cognitive functioning and locomotor behavior. Although low-level metal exposure poses a potential risk to the human nervous system, especially during the developmental stages, little is known about the effects of metal exposures on nrxn2a expression during embryonic development. We therefore exposed wild-type zebrafish embryos/larvae to cadmium (CdCl2 ), manganese (MnCl2 ), and lead ([CH3 COO]2 Pb), to determine their effect on mortality, malformation, and hatching rate...
January 24, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28045486/mimicking-neuroligin-2-functions-in-%C3%AE-cells-by-functionalized-nanoparticles-as-a-novel-approach-for-antidiabetic-therapy
#8
Anna Munder, Liron L Israel, Shirin Kahremany, Rina Ben-Shabat-Binyamini, Charles Zhang, Michal Kolitz-Domb, Olga Viskind, Anna Levine, Hanoch Senderowitz, Steven Chessler, Jean-Paul Lellouche, Arie Gruzman
Both pancreatic β-cell membranes and presynaptic active zones of neurons include in their structures similar protein complexes, which are responsible for mediating the secretion of bioactive molecules. In addition, these membrane-anchored proteins regulate interactions between neurons and guide the formation and maturation of synapses. These proteins include the neuroligins (e.g., NL-2) and their binding partners, the neurexins. The insulin secretion and maturation of β-cells is known to depend on their 3-dimensional (3D) arrangement...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28013231/neurexins-1-3-each-have-a-distinct-pattern-of-expression-in-the-early-developing-human-cerebral-cortex
#9
Lauren F Harkin, Susan J Lindsay, Yaobo Xu, Ayman Alzu'bi, Alexandra Ferrara, Emily A Gullon, Owen G James, Gavin J Clowry
Neurexins (NRXNs) are presynaptic terminal proteins and candidate neurodevelopmental disorder susceptibility genes; mutations presumably upset synaptic stabilization and function. However, analysis of human cortical tissue samples by RNAseq and quantitative real-time PCR at 8-12 postconceptional weeks, prior to extensive synapse formation, showed expression of all three NRXNs as well as several potential binding partners. However, the levels of expression were not identical; NRXN1 increased with age and NRXN2 levels were consistently higher than for NRXN3 Immunohistochemistry for each NRXN also revealed different expression patterns at this stage of development...
December 23, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27991559/shedding-of-neurexin-3%C3%AE-ectodomain-by-adam10-releases-a-soluble-fragment-that-affects-the-development-of-newborn-neurons
#10
Erika Borcel, Magda Palczynska, Marine Krzisch, Mitko Dimitrov, Giorgio Ulrich, Nicolas Toni, Patrick C Fraering
Neurexins are transmembrane synaptic cell adhesion molecules involved in the development and maturation of neuronal synapses. In the present study, we report that Nrxn3β is processed by the metalloproteases ADAM10, ADAM17, and by the intramembrane-cleaving protease γ-secretase, producing secreted neurexin3β (sNrxn3β) and a single intracellular domain (Nrxn3β-ICD). We further completed the full characterization of the sites at which Nrxn3β is processed by these proteases. Supporting the physiological relevance of the Nrxn3β processing, we demonstrate in vivo a significant effect of the secreted shedding product sNrxn3β on the morphological development of adult newborn neurons in the mouse hippocampus...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27986928/presynaptic-neuronal-pentraxin-receptor-organizes-excitatory-and-inhibitory-synapses
#11
Sung-Jin Lee, Mengping Wei, Chen Zhang, Stephan Maxeiner, ChangHui Pak, Salome Calado Botelho, Justin Trotter, Fredrik H Sterky, Thomas C Südhof
: Three neuronal pentraxins are expressed in brain, the membrane-bound 'neuronal pentraxin receptor' (NPR) and the secreted proteins NP1 and NARP (a.k.a. NP2). Neuronal pentraxins bind to AMPA-receptors at excitatory synapses, and play important, well-documented roles in the activity-dependent regulation of neural circuits via this binding activity. However, it is unknown whether neuronal pentraxins perform roles in synapses beyond modulating postsynaptic AMPA-receptor-dependent plasticity, and whether they may even act in inhibitory synapses...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27973753/vagal-nerve-stimulation-modifies-neuronal-activity-and-the-proteome-of-excitatory-synapses-of-amygdala-piriform-cortex
#12
Georgia M Alexander, Yang Zhong Huang, Erik J Soderblom, Xiao-Ping He, M Arthur Moseley, James O McNamara
Vagal Nerve Stimulation (VNS) Therapy(®) is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are unclear. We hypothesized that one mechanism involves neuronal activity-dependent modifications of central nervous system excitatory synapses. To begin to test this hypothesis, we asked whether VNS modifies the activity of neurons in amygdala and hippocampus...
December 14, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27965028/two-de-novo-mutations-in-an-autistic-child-who-had-previously-undergone-transplantation-for-dilated-cardiomyopathy-the-importance-of-keeping-an-open-mind
#13
Umair Sajid, Bob Argiropoulos, Xing-Chang Wei, Jillian S Parboosingh, Ryan E Lamont, Aneal Khan, Steven C Greenway
We report the finding of 2 de novo mutations in an 8-year-old boy with developmental delay and autism who underwent heart transplantation at 1 year of age for idiopathic dilated cardiomyopathy. We identified a de novo microdeletion at chromosome 2p16.3 involving the neurexin-1 (NRXN1) gene and a de novo pathologic variant (Pro838Leu) in the myosin heavy chain 7 (MYH7) gene. This case emphasizes the importance of comprehensive genetic evaluation in patients with cardiomyopathy, particularly if they have extracardiac abnormalities, and the necessity of interpreting variants with attention to the phenotype...
September 26, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/27960072/an-alternative-splicing-switch-shapes-neurexin-repertoires-in-principal-neurons-versus-interneurons-in-the-mouse-hippocampus
#14
Thi-Minh Nguyen, Dietmar Schreiner, Le Xiao, Lisa Traunmüller, Caroline Bornmann, Peter Scheiffele
The unique anatomical and functional features of principal and interneuron populations are critical for the appropriate function of neuronal circuits. Cell type-specific properties are encoded by selective gene expression programs that shape molecular repertoires and synaptic protein complexes. However, the nature of such programs, particularly for post-transcriptional regulation at the level of alternative splicing is only beginning to emerge. We here demonstrate that transcripts encoding the synaptic adhesion molecules neurexin-1,2,3 are commonly expressed in principal cells and interneurons of the mouse hippocampus but undergo highly differential, cell type-specific alternative splicing...
December 13, 2016: ELife
https://www.readbyqxmd.com/read/27943181/synaptogenic-assays-using-neurons-cultured-on-micropatterned-substrates
#15
Katalin Czöndör, Olivier Thoumine
One of the difficulties for studying the mechanisms of synaptogenesis stems from the spatial unpredictability of contact formation between neurons, and the involvement of many parallel adhesive pathways mediating axon/dendrite recognition. To circumvent these limitations, we describe here a method allowing the investigation of synaptic contacts at controlled locations with high precision and statistics. Specifically, primary neurons are cultured on micropatterned substrates comprising arrays of micron-scale dots coated with purified synaptogenic adhesion molecules...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27926833/conformational-plasticity-in-the-transsynaptic-neurexin-cerebellin-glutamate-receptor-adhesion-complex
#16
Shouqiang Cheng, Alpay B Seven, Jing Wang, Georgios Skiniotis, Engin Özkan
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain...
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27909399/a-subset-of-autism-associated-genes-regulate-the-structural-stability-of-neurons
#17
REVIEW
Yu-Chih Lin, Jeannine A Frei, Michaela B C Kilander, Wenjuan Shen, Gene J Blatt
Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals' ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27905548/neurexin-regulates-nighttime-sleep-by-modulating-synaptic-transmission
#18
Huawei Tong, Qian Li, Zi Chao Zhang, Yi Li, Junhai Han
Neurexins are cell adhesion molecules involved in synaptic formation and synaptic transmission. Mutations in neurexin genes are linked to autism spectrum disorders (ASDs), which are frequently associated with sleep problems. However, the role of neurexin-mediated synaptic transmission in sleep regulation is unclear. Here, we show that lack of the Drosophila α-neurexin homolog significantly reduces the quantity and quality of nighttime sleep and impairs sleep homeostasis. We report that neurexin expression in Drosophila mushroom body (MB) αβ neurons is essential for nighttime sleep...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872870/nanoscale-organization-of-synaptic-adhesion-proteins-revealed-by-single-molecule-localization-microscopy
#19
Ingrid Chamma, Florian Levet, Jean-Baptiste Sibarita, Matthieu Sainlos, Olivier Thoumine
The advent of superresolution imaging has created a strong need for both optimized labeling strategies and analysis methods to probe the nanoscale organization of complex biological structures. We present a thorough description of the distribution of synaptic adhesion proteins at the nanoscopic scale, namely presynaptic neurexin-[Formula: see text] ([Formula: see text]), and its two postsynaptic binding partners neuroligin-1 (Nlg1) and leucine-rich-repeat transmembrane protein 2 (LRRTM2). We monitored these proteins in the membrane of neurons by direct stochastic optical reconstruction microscopy, after live surface labeling with Alexa647-conjugated monomeric streptavidin...
October 2016: Neurophotonics
https://www.readbyqxmd.com/read/27871938/the-role-of-gpi-anchored-axonal-glycoproteins-in-neural-development-and-neurological-disorders
#20
REVIEW
Gianfranco Gennarini, Antonella Bizzoca, Sabrina Picocci, Daniela Puzzo, Patrizia Corsi, Andrew J W Furley
This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49...
November 18, 2016: Molecular and Cellular Neurosciences
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