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https://www.readbyqxmd.com/read/29230184/neuroligin-2-r215h-mutant-mice-manifest-anxiety-increased-prepulse-inhibition-and-impaired-spatial-learning-and-memory
#1
Chia-Hsiang Chen, Pin-Wei Lee, Hsiao-Mei Liao, Pi-Kai Chang
Neuroligin 2 (NLGN2) is a postsynaptic adhesion protein that plays an essential role in synaptogenesis and function of inhibitory neuron. We previously identified a missense mutation R215H of the NLGN2 in a patient with schizophrenia. This missense mutation was shown to be pathogenic in several cell-based assays. The objective of this study was to better understand the behavioral consequences of this mutation in vivo. We generated a line of transgenic mice carrying this mutation using a recombinant-based method...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29229842/male-homosexuality-and-maternal-immune-responsivity-to-the-y-linked-protein-nlgn4y
#2
Anthony F Bogaert, Malvina N Skorska, Chao Wang, José Gabrie, Adam J MacNeil, Mark R Hoffarth, Doug P VanderLaan, Kenneth J Zucker, Ray Blanchard
We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development-protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)-were developed...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
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/29212945/refining-the-roles-of-neuroligins-in-synapse-development-and-function-a-reductionist-conditional-knock-out-approach
#4
Hunter S Shaw, Christopher K Salmon
No abstract text is available yet for this article.
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29166241/two-classes-of-secreted-synaptic-organizers-in-the-central-nervous-system
#5
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/29123130/binding-of-mycotoxins-to-proteins-involved-in-neuronal-plasticity-a-combined-in-silico-wet-investigation
#6
Bernardina Scafuri, Antonio Varriale, Angelo Facchiano, Sabato D'Auria, Maria Elisabetta Raggi, Anna Marabotti
We have applied a combined computational procedure based on inverse and direct docking in order to identify putative protein targets of a panel of mycotoxins and xenobiotic compounds that can contaminate food and that are known to have several detrimental effects on human health. This procedure allowed us to identify a panel of human proteins as possible targets for aflatoxins, gliotoxin, ochratoxin A and deoxynivalenol. Steady-state fluorescence and microscale thermophoresis experiments allowed us to confirm the binding of some of these mycotoxins to acetylcholinesterase and X-linked neuroligin 4, two proteins involved in synapse activity and, particularly for the second protein, neuronal plasticity and development...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120426/astrocytic-neuroligins-control-astrocyte-morphogenesis-and-synaptogenesis
#7
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/29115990/dhcr24-exerts-neuroprotection-upon-inflammation-induced-neuronal-death
#8
Henna Martiskainen, Kaisa M A Paldanius, Teemu Natunen, Mari Takalo, Mikael Marttinen, Stina Leskelä, Nadine Huber, Petra Mäkinen, Enni Bertling, Hiramani Dhungana, Mikko Huuskonen, Paavo Honkakoski, Pirta Hotulainen, Kirsi Rilla, Jari Koistinaho, Hilkka Soininen, Tarja Malm, Annakaisa Haapasalo, Mikko Hiltunen
BACKGROUND: DHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer's disease. METHODS: Here, we investigated whether the overexpression of DHCR24 protects neurons against inflammation-induced neuronal death using co-cultures of mouse embryonic primary cortical neurons and BV2 microglial cells upon acute neuroinflammation...
November 7, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29107812/proteolytic-maturation-of-drosophila-neuroligin-3-by-tumor-necrosis-factor-%C3%AE-converting-enzyme-in-the-nervous-system
#9
Jun Wu, Nana Tao, Yao Tian, Guanglin Xing, Huihui Lv, Junhai Han, Chengqi Lin, Wei Xie
BACKGROUND: The functions of autism-associated Neuroligins (Nlgs) are modulated by their post-translational modifications, such as proteolytic cleavage. A previous study has shown that there are different endogenous forms of DNlg3 in Drosophila, indicating it may undergo proteolytic processing. However, the molecular mechanism underlying DNlg3 proteolytic processing is unknown. Here, we report a novel proteolytic mechanism that is essential for DNlg3 maturation and function in the nervous system...
October 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29107521/molecular-dissection-of-neuroligin-2-and-slitrk3-reveals-an-essential-framework-for-gabaergic-synapse-development
#10
Jun Li, Wenyan Han, Kenneth A Pelkey, Jingjing Duan, Xia Mao, Ya-Xian Wang, Michael T Craig, Lijin Dong, Ronald S Petralia, Chris J McBain, Wei Lu
In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM)...
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29106499/autism-related-neuroligin-4-knockout-impairs-intracortical-processing-but-not-sensory-inputs-in-mouse-barrel-cortex
#11
Petr Unichenko, Jenq-Wei Yang, Sergei Kirischuk, Sergei Kolbaev, Werner Kilb, Matthieu Hammer, Dilja Krueger-Burg, Nils Brose, Heiko J Luhmann
Neuroligin-4 (Nlgn4) is a cell adhesion protein that regulates synapse organization and function. Mutations in human NLGN4 are among the causes of autism spectrum disorders. In mouse, Nlgn4 knockout (KO) perturbs GABAergic synaptic transmission and oscillatory activity in hippocampus, and causes social interaction deficits. The complex profile of cellular and circuit changes that are caused by Nlgn4-KO is still only partly understood. Using Nlgn4-KO mice, we found that Nlgn4-KO increases the power in the alpha frequency band of spontaneous network activity in the barrel cortex under urethane anesthesia in vivo...
July 5, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29100073/synaptic-neurexin-complexes-a-molecular-code-for-the-logic-of-neural-circuits
#12
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/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/29025866/declining-levels-of-functionally-specialized-synaptic-proteins-in-plasma-neuronal-exosomes-with-progression-of-alzheimer-s-disease
#14
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/28972980/correction-functional-significance-of-rare-neuroligin-1-variants-found-in-autism
#15
Moe Nakanishi, Jun Nomura, Xiao Ji, Kota Tamada, Takashi Arai, Eiki Takahashi, Maja Bućan, Toru Takumi
[This corrects the article DOI: 10.1371/journal.pgen.1006940.].
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28959975/targeting-neuronal-activity-regulated-neuroligin-3-dependency-in-high-grade-glioma
#16
Humsa S Venkatesh, Lydia T Tam, Pamelyn J Woo, James Lennon, Surya Nagaraja, Shawn M Gillespie, Jing Ni, Damien Y Duveau, Patrick J Morris, Jean J Zhao, Craig J Thomas, Michelle Monje
High-grade gliomas (HGG) are a devastating group of cancers, and represent the leading cause of brain tumour-related death in both children and adults. Therapies aimed at mechanisms intrinsic to glioma cells have translated to only limited success; effective therapeutic strategies will need also to target elements of the tumour microenvironment that promote glioma progression. Neuronal activity promotes the growth of a range of molecularly and clinically distinct HGG types, including adult and paediatric glioblastoma (GBM), anaplastic oligodendroglioma, and diffuse intrinsic pontine glioma (DIPG)...
September 28, 2017: Nature
https://www.readbyqxmd.com/read/28958035/sleep-wake-physiology-and-quantitative-eeg-analysis-of-the-neuroligin-3-knockout-rat-model-of-autism-spectrum-disorder
#17
Alexia M Thomas, Michael D Schwartz, Michael D Saxe, Thomas S Kilduff
Study Objectives: Neuroligin-3 (NLGN3) is one of many genes associated with autism spectrum disorder (ASD). Sleep dysfunction is highly prevalent in ASD, but has not been rigorously examined in ASD models. Here, we evaluated sleep/wake physiology and behavioral phenotypes of rats with genetic ablation of Nlgn3. Methods: Male Nlgn3 knockout (KO) and wild-type (WT) rats were assessed using a test battery for ASD-related behaviors and also implanted with telemeters to record the electroencephalogram (EEG), electromyogram (EMG), body temperature, and locomotor activity...
August 31, 2017: Sleep
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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