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https://www.readbyqxmd.com/read/29323291/neurexin-controls-plasticity-of-a-mature-sexually-dimorphic-neuron
#1
Michael P Hart, Oliver Hobert
During development and adulthood, brain plasticity is evident at several levels, from synaptic structure and function to the outgrowth of dendrites and axons. Whether and how sex impinges on neuronal plasticity is poorly understood. Here we show that the sex-shared GABA (γ-aminobutyric acid)-releasing DVB neuron in Caenorhabditis elegans displays experience-dependent and sexually dimorphic morphological plasticity, characterized by the stochastic and dynamic addition of multiple neurites in adult males. These added neurites enable synaptic rewiring of the DVB neuron and instruct a functional switch of the neuron that directly modifies a step of male mating behaviour...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29281813/loss-of-synapse-repressor-mdga1-enhances-perisomatic-inhibition-confers-resistance-to-network-excitation-and-impairs-cognitive-function
#2
Steven A Connor, Ina Ammendrup-Johnsen, Yasushi Kishimoto, Parisa Karimi Tari, Vedrana Cvetkovska, Takashi Harada, Daiki Ojima, Tohru Yamamoto, Yu Tian Wang, Ann Marie Craig
Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29229705/proteolytic-processing-of-neurexins-by-presenilins-sustains-synaptic-vesicle-release
#3
Emilia Servián-Morilla, Estefanía Robles-Lanuza, Ana C Sánchez-Hidalgo, Rafael J Camacho-Garcia, Juan A Paez-Gomez, Fabiola Mavillard, Carlos A Saura, Amalia Martinez-Mir, Francisco G Scholl
Proteolytic processing of synaptic adhesion components can accommodate the function of synapses to activity-dependent changes. The adhesion system formed by Neurexins (Nrxns) and Neuroligins (Nlgns) bi-directionally orchestrate the function of pre- and postsynaptic terminals. Previous studies have shown that Presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheimer's disease, clear from glutamatergic terminals the accumulation of Neurexin C-terminal fragments (Nrxn-CTF) generated by ectodomain shedding...
December 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29221905/neurexins-and-neuropsychiatric-disorders
#4
REVIEW
Enas Kasem, Taiga Kurihara, Katsuhiko Tabuchi
Neurexins are a family of presynaptic single-pass transmembrane proteins that act as synaptic organizers in mammals. The neurexins consist of three genes (NRXN1, NRXN2, and NRXN3), each of which produces a longer α- and shorter β-form. Genomic alterations in NRXN genes have been identified in a wide variety of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, intellectual disability (ID), and addiction. Remarkably, a bi-allelic deficiency of NRXN1 was recently linked to Pitt-Hopkins syndrome...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29217522/drosophila-syd-1-has-rhogap-activity-that-is-required-for-presynaptic-clustering-of-bruchpilot-elks-but-not-neurexin-1
#5
Michael A Spinner, David A Walla, Tory G Herman
Syd-1 proteins are required for presynaptic development in worm, fly, and mouse. Syd-1s in all three species contain a Rho GTPase activating protein (GAP)-like domain of unclear significance. Invertebrate Syd-1s are thought to lack GAP activity, and mouse mSYD1A has GAP activity that is thought to be dispensible for its function. Here we show that Drosophila melanogaster Syd-1 can interact with all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development, fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly...
December 7, 2017: Genetics
https://www.readbyqxmd.com/read/29195096/role-of-neurexin2a-in-lead-induced-locomotor-defect-in-developing-zebrafish
#6
Hongwei Tu, Tao Peng, Jiaxian Liu, Xiaohui Chen, Chengji Fan, Zhibin Huang, Yiyue Zhang, Fei Zou, Xiaojing Meng
Low-dose chronic lead (Pb) exposure interferes with the development of the nervous system, which may lead to learning disabilities, behavioral abnormalities, and mental retardation. Neurexins (Nrxns) are synaptic cell-adhesion molecules associated with neurological disorders. We hypothesized that Pb can affect the expression of nrxns during synapse formation and alter the phenotype behavior. Here, apoptosis, nrxns mRNA expression, and alterations of locomotion were examined after exposure to Pb in zebrafish embryos/larvae...
November 22, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29166241/two-classes-of-secreted-synaptic-organizers-in-the-central-nervous-system
#7
Michisuke Yuzaki
Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of preand/ or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft...
November 20, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29160301/new-insights-into-the-pharmacogenomics-of-antidepressant-response-from-the-gendep-and-star-d-studies-rare-variant-analysis-and-high-density-imputation
#8
C Fabbri, K E Tansey, R H Perlis, J Hauser, N Henigsberg, W Maier, O Mors, A Placentino, M Rietschel, D Souery, G Breen, C Curtis, L Sang-Hyuk, S Newhouse, H Patel, M Guipponi, N Perroud, G Bondolfi, M O'Donovan, G Lewis, J M Biernacka, R M Weinshilboum, A Farmer, K J Aitchison, I Craig, P McGuffin, R Uher, C M Lewis
Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29120426/astrocytic-neuroligins-control-astrocyte-morphogenesis-and-synaptogenesis
#9
Jeff A Stogsdill, Juan Ramirez, Di Liu, Yong Ho Kim, Katherine T Baldwin, Eray Enustun, Tiffany Ejikeme, Ru-Rong Ji, Cagla Eroglu
Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins...
November 8, 2017: Nature
https://www.readbyqxmd.com/read/29100073/synaptic-neurexin-complexes-a-molecular-code-for-the-logic-of-neural-circuits
#10
REVIEW
Thomas C Südhof
Synapses are specialized junctions between neurons in brain that transmit and compute information, thereby connecting neurons into millions of overlapping and interdigitated neural circuits. Here, we posit that the establishment, properties, and dynamics of synapses are governed by a molecular logic that is controlled by diverse trans-synaptic signaling molecules. Neurexins, expressed in thousands of alternatively spliced isoforms, are central components of this dynamic code. Presynaptic neurexins regulate synapse properties via differential binding to multifarious postsynaptic ligands, such as neuroligins, cerebellin/GluD complexes, and latrophilins, thereby shaping the input/output relations of their resident neural circuits...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/29079805/genetic-interaction-of-disc1-and-neurexin-in-the-development-of-fruit-fly-glutamatergic-synapses
#11
Himani Pandey, Katia Bourahmoune, Takato Honda, Ken Honjo, Kazuki Kurita, Tomohito Sato, Akira Sawa, Katsuo Furukubo-Tokunaga
Originally identified at the breakpoint of a (1;11)(q42.1; q14.3) chromosomal translocation in a Scottish family with a wide range of mental disorders, the DISC1 gene has been a focus of intensive investigations as an entry point to study the molecular mechanisms of diverse mental dysfunctions. Perturbations of the DISC1 functions lead to behavioral changes in animal models, which are relevant to psychiatric conditions in patients. In this work, we have expressed the human DISC1 gene in the fruit fly (Drosophila melanogaster) and performed a genetic screening for the mutations of psychiatric risk genes that cause modifications of DISC1 synaptic phenotypes at the neuromuscular junction...
October 27, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/29045040/neurexin-gene-family-variants-as-risk-factors-for-autism-spectrum-disorder
#12
Jia Wang, Jianhua Gong, Li Li, Yanlin Chen, Lingfei Liu, HuaiTing Gu, Xiu Luo, Fang Hou, Jiajia Zhang, Ranran Song
Increasing evidence suggests that abnormal synaptic function leads to neuronal developmental disorders and is an important component of the etiology of autism spectrum disorder (ASD). Neurexins are presynaptic cell-adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals. Thus, neurexins are attractive candidate genes for autism. Since gene families have greater power to reveal genetic association than single genes, we designed this case-control study to investigate six genetic variants in three neurexin genes (NRXN1, NRXN2, and NRXN3) in a Chinese population including 529 ASD patients and 1,923 healthy controls...
October 16, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/29028156/genetic-background-effects-in-neuroligin-3-mutant-mice-minimal-behavioral-abnormalities-on-c57-background
#13
Thomas C Jaramillo, Christine Ochoa Escamilla, Shunan Liu, Lauren Peca, Shari G Birnbaum, Craig M Powell
Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein that interacts with presynaptic ligands including neurexin-1 (NRXN1) [Ichtchenko et al., Journal of Biological Chemistry, 271, 2676-2682, 1996]. Mice harboring a mutation in the NLGN3 gene (NL3R451C) mimicking a mutation found in two brothers with autism spectrum disorder (ASD) were previously generated and behaviorally phenotyped for autism-related behaviors. In these NL3R451C mice generated and tested on a hybrid C57BL6J/129S2/SvPasCrl background, we observed enhanced spatial memory and reduced social interaction [Tabuchi et al...
October 13, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/29028155/a-parallel-reaction-monitoring-mass-spectrometric-method-for-analysis-of-potential-csf-biomarkers-for-alzheimer-s-disease
#14
Gunnar Brinkmalm, Simon Sjödin, Anja Hviid Simonsen, Steen Gregers Hasselbalch, Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow
PURPOSE: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and 2-3 peptides per protein were quantified using stable isotope-labeled peptide standards...
October 13, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29025866/declining-levels-of-functionally-specialized-synaptic-proteins-in-plasma-neuronal-exosomes-with-progression-of-alzheimer-s-disease
#15
Edward J Goetzl, Erin L Abner, Gregory A Jicha, Dimitrios Kapogiannis, Janice B Schwartz
Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2α (NRXN2α), with their respective postsynaptic functional partners, GluA4-containing glutamate (AMPA4) receptor and neuroligin 1 (NLGN1), enhance excitatory synaptic activity in some areas of the hippocampus and cerebral cortex. As early damage of such excitatory circuits in the brain tissues of participants with Alzheimer's disease (AD) correlates with cognitive losses, plasma neuron-derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics...
October 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28975140/patient-derived-hipsc-neurons-with-heterozygous-cntnap2-deletions-display-altered-neuronal-gene-expression-and-network-activity
#16
Erin Flaherty, Rania M Deranieh, Elena Artimovich, Inkyu S Lee, Arthur J Siegel, Deborah L Levy, Michael W Nestor, Kristen J Brennand
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28970473/patient-derived-hipsc-neurons-with-heterozygous-cntnap2-deletions-display-altered-neuronal-gene-expression-and-network-activity
#17
Erin Flaherty, Rania M Deranieh, Elena Artimovich, Inkyu S Lee, Arthur J Siegel, Deborah L Levy, Michael W Nestor, Kristen J Brennand
Variants in CNTNAP2, a member of the neurexin family of genes that function as cell adhesion molecules, have been associated with multiple neuropsychiatric conditions such as schizophrenia, autism spectrum disorder and intellectual disability; animal studies indicate a role for CNTNAP2 in axon guidance, dendritic arborization and synaptogenesis. We previously reprogrammed fibroblasts from a family trio consisting of two carriers of heterozygous intragenic CNTNAP2 deletions into human induced pluripotent stem cells (hiPSCs) and described decreased migration in the neural progenitor cells (NPCs) differentiated from the affected CNTNAP2 carrier in this trio...
October 2, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28957672/structural-mechanism-for-modulation-of-synaptic-neuroligin-neurexin-signaling-by-mdga-proteins
#18
Jonathan Elegheert, Vedrana Cvetkovska, Amber J Clayton, Christina Heroven, Kristel M Vennekens, Samuel N Smukowski, Michael C Regan, Wanyi Jia, Alexandra C Smith, Hiro Furukawa, Jeffrey N Savas, Joris de Wit, Jo Begbie, Ann Marie Craig, A Radu Aricescu
No abstract text is available yet for this article.
September 27, 2017: Neuron
https://www.readbyqxmd.com/read/28948087/not-all-neuroligin-3-and-4x-missense-variants-lead-to-significant-functional-inactivation
#19
Xiaojuan Xu, Zhengmao Hu, Lusi Zhang, Hongfang Liu, Yuemei Cheng, Kun Xia, Xuehong Zhang
INTRODUCTION: Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28939043/neuroligin-induced-presynaptic-differentiation-through-slm2-mediated-splicing-modifications-of-neurexin-in-cerebellar-cultures
#20
Yuji Sato, Satoko Suzuki, Yoko Iijima, Takatoshi Iijima
Neurexins (NRXs) and neuroligins (NLs) play important roles in synapse specification. The alternatively spliced segment 4 (AS4) of NRX genes (Nrxn) is a critical element in selective trans-synaptic interactions. However, the role of splicing of NRXs and NLs in synapse specification is not fully understood. To investigate the exact role of splice-dependent NRX-NL interaction in the specification of glutamatergic and gamma-aminobutyric acid (GABA)-ergic synapses in the cerebellum, we evaluated the synaptogenic receptor activity of NL1/2/3 isoforms in a neuron-fibroblast co-culture system, in which the Nrxn AS4 segments are manipulated using SLM2, a selective and dominant regulator of AS4 splicing...
November 18, 2017: Biochemical and Biophysical Research Communications
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