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https://www.readbyqxmd.com/read/28515678/soluble-ectodomain-of-neuroligin-1-decreases-synaptic-activity-by-activating-metabotropic-glutamate-receptor-2
#1
Michelle D Gjørlund, Eva M M Carlsen, Andreas B Kønig, Oksana Dmytrieva, Anders V Petersen, Jacob Jacobsen, Vladimir Berezin, Jean-François Perrier, Sylwia Owczarek
Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are located primarily at the periphery of presynaptic terminals, where they inhibit the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress the release of glutamate and decrease synaptic transmission...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28498949/proteolytic-cleavage-is-required-for-functional-neuroligin-2-maturation-and-trafficking-in-drosophila
#2
Renjun Tu, Jinjun Qian, Menglong Rui, Nana Tao, Mingkuan Sun, Yan Zhuang, Huihui Lv, Junhai Han, Moyi Li, Wei Xie
Neuroligins are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Neuroligins are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Neuroligin maturation and trafficking have remained largely unknown. Here, we found that Drosophila Neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages...
May 11, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28450540/aplp1-is-a-synaptic-cell-adhesion-molecule-supporting-maintenance-of-dendritic-spines-and-basal-synaptic-transmission
#3
Sandra Schilling, Annika Mehr, Susann Ludewig, Jonathan Stephan, Marius Zimmermann, Alexander August, Paul Strecker, Martin Korte, Edward H Koo, Ulrike Müller, Stefan Kins, Simone Eggert
The amyloid precursor protein (APP), a key player in Alzheimer's disease, belongs to the family of synaptic adhesion molecules (SAM's) due to its impact on synapse formation and synaptic plasticity. These functions are mediated by both, the secreted ectodomain (sAPP) that acts as a neurotrophic factor and full-length APP forming trans-cellular dimers. Two homologues of APP exist in mammals, the APP like proteins, APLP1 and APLP2, exhibiting partly overlapping functions to APP. Here we tested if APLP1 and APLP2 also show features of SAMs...
April 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28434869/worms-on-the-spectrum-c-elegans-models-in-autism-research
#4
REVIEW
Kathrin Schmeisser, J Alex Parker
The small non-parasitic nematode Caenorhabditis elegans is widely used in neuroscience thanks to its well-understood development and lineage of the nervous system. Furthermore, C. elegans has been used to model many human developmental and neurological conditions to better understand disease mechanisms and identify potential therapeutic strategies. Autism spectrum disorder (ASD) is the most prevalent of all neurodevelopmental disorders, and the C. elegans system may provide opportunities to learn more about this complex disorder...
April 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28385162/neuroligin-3-r451c-mutation-alters-electroencephalography-spectral-activity-in-an-animal-model-of-autism-spectrum-disorders
#5
Jackie J Liu, Kevin P Grace, Richard L Horner, Miguel A Cortez, Yiwen Shao, Zhengping Jia
Human studies demonstrate that sleep impairment is a concurrent comorbidity of autism spectrum disorders (ASD), but its etiology remains largely uncertain. One of the prominent theories of ASD suggests that an imbalance in synaptic excitation/inhibition may contribute to various aspects of ASD, including sleep impairments. Following the identification of Nlgn3(R451C) mutation in patients with ASD, its effects on synaptic transmission and social behaviours have been examined extensively in the mouse model. However, the contributory role of this mutation to sleep impairments in ASD remains unknown...
April 7, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28366281/neurexin-restricts-axonal-branching-in-columns-by-promoting-ephrin-clustering
#6
Lina Liu, Yao Tian, Xiao-Yan Zhang, Xinwang Zhang, Tao Li, Wei Xie, Junhai Han
Columnar restriction of neurites is critical for forming nonoverlapping receptive fields and preserving spatial sensory information from the periphery in both vertebrate and invertebrate nervous systems, but the underlying molecular mechanisms remain largely unknown. Here, we demonstrate that Drosophila homolog of α-neurexin (DNrx) plays an essential role in columnar restriction during L4 axon branching. Depletion of DNrx from L4 neurons resulted in misprojection of L4 axonal branches into neighboring columns due to impaired ephrin clustering...
April 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28362857/a-novel-synaptic-junction-preparation-for-the-identification-and-characterization-of-cleft-proteins
#7
Amelia Burch, Jung-Hwa Tao-Cheng, Ayse Dosemeci
Identification of synaptic cleft components has been hampered by the lack of a suitable preparation enriched in synaptic junctions devoid of adjoining peripheral membranes. Prior strategies for the isolation of synaptic junctions, relying on detergents for the removal of peripheral membranes, resulted in substantial loss of membranes lining the cleft. Here, a novel, detergent-free method is described for the preparation of a synaptic junction (SJ) fraction, using phospholipase A2. Limited digestion of synaptic plasma membrane (SPM) fraction with phospholipase A2 followed by centrifugation over a sucrose cushion results in selective removal of membranes peripheral to the cleft while junctional membranes remain relatively intact as observed by electron microscopy...
2017: PloS One
https://www.readbyqxmd.com/read/28297673/%C3%AE-protocadherins-interact-with-neuroligin-1-and-negatively-regulate-dendritic-spine-morphogenesis
#8
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-amyloid-%C3%AE-a%C3%AE-oligomers-with-neurexin-2%C3%AE-and-neuroligin-1-mediates-synapse-damage-and-memory-loss-in-mice
#9
Jordano Brito-Moreira, Mychael V Lourenco, Mauricio M Oliveira, Felipe C Ribeiro, José Henrique Ledo, Luan P Diniz, Juliana F S Vital, 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 may 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 associated recently with AD...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28279354/garlh-family-proteins-stabilize-gabaa-receptors-at-synapses
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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