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https://www.readbyqxmd.com/read/28297673/%C3%AE-protocadherins-interact-with-neuroligin-1-and-negatively-regulate-dendritic-spine-morphogenesis
#1
Michael J Molumby, Rachel M Anderson, Dillan J Newbold, Norah K Koblesky, Andrew M Garrett, Dietmar Schreiner, Jason J Radley, Joshua A Weiner
The 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules are critical for the elaboration of complex dendritic arbors in the cerebral cortex. Here, we provide evidence that the γ-Pcdhs negatively regulate synapse development by inhibiting the postsynaptic cell adhesion molecule, neuroligin-1 (Nlg1). Mice lacking all γ-Pcdhs in the forebrain exhibit significantly increased dendritic spine density in vivo, while spine density is significantly decreased in mice overexpressing one of the 22 γ-Pcdh isoforms...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28283575/interaction-of-a%C3%AE-oligomers-with-neurexin-2%C3%AE-and-neuroligin-1-mediates-synapse-damage-and-memory-loss-in-mice
#2
Jordano Brito-Moreira, Mychael V Lourenco, Mauricio M Oliveira, Juliana F S Vital, Felipe C Ribeiro, José Henrique Ledo, Luan P Diniz, Margaret H Magdesian, Helen M Melo, Fernanda Barros-Aragão, Jorge M de Souza, Soniza V Alves-Leon, Flavia C A Gomes, Julia R Clarke, Cláudia P Figueiredo, Fernanda G De Felice, Sergio T Ferreira
Brain accumulation of the amyloid-β protein (Aβ) and synapse loss are neuropathological hallmarks of Alzheimer disease (AD). Aβ oligomers (AβOs) are synaptotoxins that build up in the brains of patients and are thought to contribute to memory impairment in AD. Thus, identification of novel synaptic components that are targeted by AβOs will likely contribute to the elucidation of disease-relevant mechanisms. Trans-synaptic interactions between neurexins (Nrxs) and neuroligins (NLs) are essential for synapse structure, stability and function, and reduced NL levels have been recently associated with AD...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28279354/garlh-family-proteins-stabilize-gabaa-receptors-at-synapses
#3
Tokiwa Yamasaki, Erika Hoyos-Ramirez, James S Martenson, Megumi Morimoto-Tomita, Susumu Tomita
Ionotropic neurotransmitter receptors mediate fast synaptic transmission by functioning as ligand-gated ion channels. Fast inhibitory transmission in the brain is mediated mostly by ionotropic GABAA receptors (GABAARs), but their essential components for synaptic localization remain unknown. Here, we identify putative auxiliary subunits of GABAARs, which we term GARLHs, consisting of LH4 and LH3 proteins. LH4 forms a stable tripartite complex with GABAARs and neuroligin-2 in the brain. Moreover, LH4 is required for the synaptic localization of GABAARs and inhibitory synaptic transmission in the hippocampus...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28265586/forced-neuronal-interactions-cause-poor-communication
#4
Marine Krzisch, Nicolas Toni
Post-natal hippocampal neurogenesis plays a role in hippocampal function, and neurons born post-natally participate to spatial memory and mood control. However, a great proportion of granule neurons generated in the post-natal hippocampus are eliminated during the first 3 weeks of their maturation, a mechanism that depends on their synaptic integration. In a recent study, we examined the possibility of enhancing the synaptic integration of neurons born post-natally, by specifically overexpressing synaptic cell adhesion molecules in these cells...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28255463/social-isolation-alters-social-and-mating-behavior-in-the-r451c-neuroligin-mouse-model-of-autism
#5
E L Burrows, A F Eastwood, C May, S C Kolbe, T Hill, N M McLachlan, L Churilov, A J Hannan
Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in male NL3(R451C) and WT mice...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28255461/dynamic-control-of-synaptic-adhesion-and-organizing-molecules-in-synaptic-plasticity
#6
REVIEW
Gabby Rudenko
Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, forming trans-complexes spanning the synaptic cleft or cis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28194405/abundance-and-significance-of-neuroligin-1-and-neurexin-ii-in-the-enteric-nervous-system-of-embryonic-rats
#7
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/28128356/graphene-oxide-dysregulates-neuroligin-nlg-1-mediated-molecular-signaling-in-interneurons-in-caenorhabditis-elegans
#8
He Chen, Huirong Li, Dayong Wang
Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123011/the-role-of-neuroligins-in-the-cerebellum-highlights-the-diversity-of-synapse-specifying-molecules
#9
Jessica Messier
No abstract text is available yet for this article.
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28067903/modulation-of-excitation-on-parvalbumin-interneurons-by-neuroligin-3-regulates-the-hippocampal-network
#10
Jai S Polepalli, Hemmings Wu, Debanjan Goswami, Casey H Halpern, Thomas C Südhof, Robert C Malenka
Hippocampal network activity is generated by a complex interplay between excitatory pyramidal cells and inhibitory interneurons. Although much is known about the molecular properties of excitatory synapses on pyramidal cells, comparatively little is known about excitatory synapses on interneurons. Here we show that conditional deletion of the postsynaptic cell adhesion molecule neuroligin-3 in parvalbumin interneurons causes a decrease in NMDA-receptor-mediated postsynaptic currents and an increase in presynaptic glutamate release probability by selectively impairing the inhibition of glutamate release by presynaptic Group III metabotropic glutamate receptors...
February 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28045486/mimicking-neuroligin-2-functions-in-%C3%AE-cells-by-functionalized-nanoparticles-as-a-novel-approach-for-antidiabetic-therapy
#11
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/27943181/synaptogenic-assays-using-neurons-cultured-on-micropatterned-substrates
#12
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/27872870/nanoscale-organization-of-synaptic-adhesion-proteins-revealed-by-single-molecule-localization-microscopy
#13
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/27869801/direct-dorsal-hippocampal-prelimbic-cortex-connections-strengthen-fear-memories
#14
Xiaojing Ye, Dana Kapeller-Libermann, Alessio Travaglia, M Carmen Inda, Cristina M Alberini
The ability to regulate the consolidation and strengthening of memories for threatening experiences is critical for mental health, and its dysregulation may lead to psychopathologies. Re-exposure to the context in which the threat was experienced can either increase or decrease fear response through distinct processes known, respectively, as reconsolidation or extinction. Using a context retrieval-dependent memory-enhancement model in rats, we report that memory strengthens through activation of direct projections from dorsal hippocampus to prelimbic (PL) cortex and activation of critical PL molecular mechanisms that are not required for extinction...
January 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/27865048/neuroligin-2-nonsense-variant-associated-with-anxiety-autism-intellectual-disability-hyperphagia-and-obesity
#15
Daniel J Parente, Caryn Garriga, Berivan Baskin, Ganka Douglas, Megan T Cho, Gabriel C Araujo, Marwan Shinawi
Neuroligins are post-synaptic, cellular adhesion molecules implicated in synaptic formation and function. NLGN2 is strongly linked to inhibitory, GABAergic signaling and is crucial for maintaining the excitation-inhibition balance in the brain. Disruption of the excitation-inhibition balance is associated with neuropsychiatric disease. In animal models, altered NLGN2 expression causes anxiety, developmental delay, motor discoordination, social impairment, aggression, and sensory processing defects. In humans, mutations in NLGN3 and NLGN4 are linked to autism and schizophrenia; NLGN2 missense variants are implicated in schizophrenia...
January 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27805570/distinct-roles-for-extracellular-and-intracellular-domains-in-neuroligin-function-at-inhibitory-synapses
#16
Quynh-Anh Nguyen, Meryl E Horn, Roger A Nicoll
Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses...
November 2, 2016: ELife
https://www.readbyqxmd.com/read/27782075/association-analysis-of-noncoding-variants-in-neuroligins-3-and-4x-genes-with-autism-spectrum-disorder-in-an-italian-cohort
#17
Martina Landini, Ivan Merelli, M Elisabetta Raggi, Nadia Galluccio, Francesca Ciceri, Arianna Bonfanti, Serena Camposeo, Angelo Massagli, Laura Villa, Erika Salvi, Daniele Cusi, Massimo Molteni, Luciano Milanesi, Anna Marabotti, Alessandra Mezzelani
Since involved in synaptic transmission and located on X-chromosome, neuroligins 3 and 4X have been studied as good positional and functional candidate genes for autism spectrum disorder pathogenesis, although contradictory results have been reported. Here, we performed a case-control study to assess the association between noncoding genetic variants in NLGN3 and NLGN4X genes and autism, in an Italian cohort of 202 autistic children analyzed by high-resolution melting. The results were first compared with data from 379 European healthy controls (1000 Genomes Project) and then with those from 1061 Italian controls genotyped by Illumina single nucleotide polymorphism (SNP) array 1M-duo...
October 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27725662/developmental-plasticity-shapes-synaptic-phenotypes-of-autism-associated-neuroligin-3-mutations-in-the-calyx-of-held
#18
B Zhang, E Seigneur, P Wei, O Gokce, J Morgan, T C Südhof
Neuroligins are postsynaptic cell-adhesion molecules that bind to presynaptic neurexins. Mutations in neuroligin-3 predispose to autism, but how such mutations affect synaptic function remains incompletely understood. Here we systematically examined the effect of three autism-associated mutations, the neuroligin-3 knockout, the R451C knockin, and the R704C knockin, on synaptic transmission in the calyx of Held, a central synapse ideally suited for high-resolution analyses of synaptic transmission. Surprisingly, germline knockout of neuroligin-3 did not alter synaptic transmission, whereas the neuroligin-3 R451C and R704C knockins decreased and increased, respectively, synaptic transmission...
October 11, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27717669/the-lgi1-adam22-protein-complex-in-synaptic-transmission-and-synaptic-disorders
#19
Yuko Fukata, Norihiko Yokoi, Yuri Miyazaki, Masaki Fukata
Physiological functioning of the brain requires fine-tuned synaptic transmission, and its dysfunction causes various brain disorders such as autism, dementia, and epilepsy. It is therefore extremely important to identify and characterize key regulators of synaptic function. In particular, disease-related synaptic proteins, such as autism-related neurexin-neuroligin and psychiatric disorder-related NMDA receptor, have attracted considerable attention. Recent basic and clinical research has highlighted critical roles of a ligand-receptor complex, LGI1-ADAM22, in synaptic transmission and brain function, as mutations in the LGI1 gene cause autosomal dominant lateral temporal lobe epilepsy and autoantibodies to LGI1 cause limbic encephalitis which is characterized by memory loss and seizures...
October 4, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27697534/emerging-roles-of-the-neurotrophin-receptor-trkc-in-synapse-organization
#20
Yusuke Naito, Alfred Kihoon Lee, Hideto Takahashi
Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ)...
September 30, 2016: Neuroscience Research
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