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https://www.readbyqxmd.com/read/29028156/genetic-background-effects-in-neuroligin-3-mutant-mice-minimal-behavioral-abnormalities-on-c57-background
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28921757/the-neurobiological-bases-of-autism-spectrum-disorders-the-r451c-neuroligin-3-mutation-hampers-the-expression-of-long-term-synaptic-depression-in-the-dorsal-striatum
#9
Giuseppina Martella, Maria Meringolo, Laura Trobiani, Antonella De Jaco, Antonio Pisani, Paola Bonsi
Autism spectrum disorders (ASDs) comprise a heterogeneous group of disorders with a complex genetic etiology. Current theories on the pathogenesis of ASDs suggest that they might arise from an aberrant synaptic transmission affecting specific brain circuits and synapses. The striatum, which is part of the basal ganglia circuit, is one of the brain regions involved in ASDs. Mouse models of ASDs have provided evidence for an imbalance between excitatory and inhibitory neurotransmission. Here we investigated the expression of long-term synaptic plasticity at corticostriatal glutamatergic synapses in the dorsal striatum of the R451C-NL3 phenotypic mouse model of autism...
September 16, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28912273/neuroligin-4-regulates-synaptic-growth-via-the-bone-morphogenetic-protein-bmp-signaling-pathway-at-the-drosophila-neuromuscular-junction
#10
Xinwang Zhang, Menglong Rui, Guangmin Gan, Cong Huang, Jukang Yi, Huihui Lv, Wei Xie
The neuroligin (Nlg) family of neural cell adhesion molecules is thought to be required for synapse formation and development, and has been linked to the development of autism spectrum disorders in humans. In Drosophila melanogaster, mutations in the neuroligin 1-3 genes have been reported to induce synapse developmental defects at neuromuscular junctions (NMJs), but the role of neuroligin 4 (dnlg4) in synapse development has not been determined. Here, we report that the Drosophila neuroligin 4 (DNlg4) is different from DNlg1-3 that it presynaptically regulates NMJ synapse development...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28879499/impaired-dopamine-dependent-locomotory-behavior-of-c-elegans-neuroligin-mutants-depends-on-the-catechol-o-methyltransferase-comt-4
#11
Ángel Rodríguez-Ramos, M Mar Gámez-Del-Estal, Montserrat Porta-de-la-Riva, Julián Cerón, Manuel Ruiz-Rubio
Neurexins and neuroligins are neuronal membrane adhesion molecules that have been involved in neuropsychiatric and neurodevelopmental disorders. The nrx-1 and nlg-1 genes of Caenorhabditis elegans encode NRX-1 and NLG-1, orthologue proteins of human neurexins and neuroligins, respectively. Dopaminergic and serotoninergic signalling control the locomotory rate of the nematode. When well-fed animals are transferred to a plate with food (bacterial lawn), they reduce the locomotory rate. This behavior, which depends on dopamine, is known as basal slowing response (BSR)...
September 6, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28875935/golgi-independent-secretory-trafficking-through-recycling-endosomes-in-neuronal-dendrites-and-spines
#12
Aaron B Bowen, Ashley M Bourke, Brian G Hiester, Cyril Hanus, Matthew J Kennedy
Neurons face the challenge of regulating the abundance, distribution and repertoire of integral membrane proteins within their immense, architecturally complex dendritic arbors. While the endoplasmic reticulum (ER) supports dendritic translation, most dendrites lack the Golgi apparatus (GA), an essential organelle for conventional secretory trafficking. Thus, whether secretory cargo is locally trafficked in dendrites through a non-canonical pathway remains a fundamental question. Here we define the dendritic trafficking itinerary for key synaptic molecules in rat cortical neurons...
September 6, 2017: ELife
https://www.readbyqxmd.com/read/28841651/functional-significance-of-rare-neuroligin-1-variants-found-in-autism
#13
Moe Nakanishi, Jun Nomura, Xiao Ji, Kota Tamada, Takashi Arai, Eiki Takahashi, Maja Bućan, Toru Takumi
Genetic mutations contribute to the etiology of autism spectrum disorder (ASD), a common, heterogeneous neurodevelopmental disorder characterized by impairments in social interaction, communication, and repetitive and restricted patterns of behavior. Since neuroligin3 (NLGN3), a cell adhesion molecule at the neuronal synapse, was first identified as a risk gene for ASD, several additional variants in NLGN3 and NLGN4 were found in ASD patients. Moreover, synaptopathies are now known to cause several neuropsychiatric disorders including ASD...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28817804/structural-mechanism-for-modulation-of-synaptic-neuroligin-neurexin-signaling-by-mdga-proteins
#14
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
Neuroligin-neurexin (NL-NRX) complexes are fundamental synaptic organizers in the central nervous system. An accurate spatial and temporal control of NL-NRX signaling is crucial to balance excitatory and inhibitory neurotransmission, and perturbations are linked with neurodevelopmental and psychiatric disorders. MDGA proteins bind NLs and control their function and interaction with NRXs via unknown mechanisms. Here, we report crystal structures of MDGA1, the NL1-MDGA1 complex, and a spliced NL1 isoform. Two large, multi-domain MDGA molecules fold into rigid triangular structures, cradling a dimeric NL to prevent NRX binding...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817794/a-triad-of-crystals-sheds-light-on-mdga-interference-with-neuroligation
#15
Olivier Thoumine, Pascale Marchot
Neurexins and neuroligins form trans-synaptic complexes that promote synapse development. In this issue of Neuron, Aricescu and colleagues (Elegheert et al., 2017) complement and strengthen two recent reports by the Kim and Rudenko teams (Kim et al., 2017; Gangwar et al., 2017) to dissect the molecular determinants by which MDGAs challenge the neurexin-neuroligin partnership.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28816653/assembly-rules-for-gabaa-receptor-complexes-in-the-brain
#16
James S Martenson, Tokiwa Yamasaki, Nashid H Chaudhury, David Albrecht, Susumu Tomita
GABAA receptor (GABAAR) pentamers are assembled from a pool of 19 subunits, and variety in subunit combinations diversifies GABAAR functions to tune brain activity. Pentamers with distinct subunit compositions localize differentially at synaptic and non-synaptic sites to mediate phasic and tonic inhibition, respectively. Despite multitudes of theoretical permutations, limited subunit combinations have been identified in the brain. Currently, no molecular model exists for combinatorial GABAAR assembly in vivo...
August 17, 2017: ELife
https://www.readbyqxmd.com/read/28795135/male-and-female-mice-lacking-neuroligin-3-modify-the-behavior-of-their-wild-type-littermates
#17
Shireene Kalbassi, Sven O Bachmann, Ellen Cross, Victoria H Roberton, Stéphane J Baudouin
In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other's behavior. We have found that, when raised together, male Nlgn3 knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male Nlgn3 knockout mice correlated with an increase in their anxiety...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28740469/neuroligins-nlg2-and-nlg4-affect-social-behavior-in-drosophila-melanogaster
#18
Kristina Corthals, Alina Sophia Heukamp, Robert Kossen, Isabel Großhennig, Nina Hahn, Heribert Gras, Martin C Göpfert, Ralf Heinrich, Bart R H Geurten
The genome of Drosophila melanogaster includes homologs to approximately one-third of the currently known human disease genes. Flies and humans share many biological processes, including the principles of information processing by excitable neurons, synaptic transmission, and the chemical signals involved in intercellular communication. Studies on the molecular and behavioral impact of genetic risk factors of human neuro-developmental disorders [autism spectrum disorders (ASDs), schizophrenia, attention deficit hyperactivity disorders, and Tourette syndrome] increasingly use the well-studied social behavior of D...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28708891/loss-of-neuroligin3-specifically-downregulates-retinal-gabaa%C3%AE-2-receptors-without-abolishing-direction-selectivity
#19
Mrinalini Hoon, Vidhyasankar Krishnamoorthy, Tim Gollisch, Bjoern Falkenburger, Frederique Varoqueaux
The postsynaptic adhesion proteins Neuroligins (NLs) are essential for proper synapse function, and their alterations are associated with a variety of neurodevelopmental disorders. It is increasingly clear that each NL isoform occupies specific subsets of synapses and is able to regulate the function of discrete networks. Studies of NL2 and NL4 in the retina in particular have contributed towards uncovering their role in inhibitory synapse function. In this study we show that NL3 is also predominantly expressed at inhibitory postsynapses in the retinal inner plexiform layer (IPL), where it colocalizes with both GABAA- and glycinergic receptor clusters in a 3:2 ratio...
2017: PloS One
https://www.readbyqxmd.com/read/28695613/ngl-3-induced-presynaptic-differentiation-of-hippocampal-neurons-in-an-afadin-dependent-nectin-1-independent-manner
#20
Tomohiko Maruo, Kenji Mandai, Muneaki Miyata, Shotaro Sakakibara, Shujie Wang, Kousyoku Sai, Yu Itoh, Aika Kaito, Takeshi Fujiwara, Akira Mizoguchi, Yoshimi Takai
A hippocampal mossy fiber synapse, which is implicated in learning and memory, has a complex structure. We have previously shown using afadin-deficient mice that afadin plays multiple roles in the structural and functional differentiations of this synapse. We investigated here using a co-culture system with cultured hippocampal neurons and non-neuronal COS-7 cells expressing synaptogenic cell adhesion molecules (CAMs) whether afadin is involved in the presynaptic differentiation of hippocampal synapses. Postsynaptic CAMs NGL-3 (alias, a Lrrc4b gene product) and neuroligin induced presynaptic differentiation by trans-interacting with their respective presynaptic binding CAMs LAR (alias, a Ptprf gene product) and neurexin...
July 11, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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