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https://www.readbyqxmd.com/read/28708891/loss-of-neuroligin3-specifically-downregulates-retinal-gabaa%C3%AE-2-receptors-without-abolishing-direction-selectivity
#1
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
#2
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
https://www.readbyqxmd.com/read/28669545/retrograde-synaptic-inhibition-is-mediated-by-%C3%AE-neurexin-binding-to-the-%C3%AE-2%C3%AE-subunits-of-n-type-calcium-channels
#3
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M Kaplan
The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/α2δ), decreasing UNC-36 abundance at pre-synaptic elements...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28656720/down-regulation-of-fibronectin-and-the-correlated-expression-of-neuroligin-in-hirschsprung-disease
#4
Y Zheng, X Lv, D Wang, N Gao, Q Zhang, A Li
AIM: The goal of this study was to investigate the expression of fibronectin (FN) and the correlated abundance of neuroligins (NLs) in the enteric nervous system (ENS) and to find a novel diagnostic marker in the serum of Hirschsprung disease (HSCR) patients. METHODS: The expression levels of FN, neuroligin-1 and neuroligin-2 were detected in 114 children with or without HSCR. The expression and localization of the NLs and FN were assessed morphologically by immunohistochemical staining...
June 28, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28643105/differential-role-of-gabaa-receptors-and-neuroligin-2-for-perisomatic-gabaergic-synapse-formation-in-the-hippocampus
#5
Patrizia Panzanelli, Simon Früh, Jean-Marc Fritschy
Perisomatic GABAergic synapses onto hippocampal pyramidal cells arise from two populations of basket cells with different neurochemical and functional properties. The presence of the dystrophin-glycoprotein complex in their postsynaptic density (PSD) distinguishes perisomatic synapses from GABAergic synapses on dendrites and the axon-initial segment. Targeted deletion of neuroligin 2 (NL2), a transmembrane protein interacting with presynaptic neurexin, has been reported to disrupt postsynaptic clustering of GABAA receptors (GABAAR) and their anchoring protein, gephyrin, at perisomatic synapses...
June 22, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28641112/molecular-mechanism-of-mdga1-regulation-of-neuroligin-2-neurexin-trans-synaptic-bridges
#6
Shanti Pal Gangwar, Xiaoying Zhong, Suchithra Seshadrinathan, Hui Chen, Mischa Machius, Gabby Rudenko
Neuroligins and neurexins promote synapse development and validation by forming trans-synaptic bridges spanning the synaptic cleft. Select pairs promote excitatory and inhibitory synapses, with neuroligin 2 (NLGN2) limited to inhibitory synapses and neuroligin 1 (NLGN1) dominating at excitatory synapses. The cell-surface molecules, MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) and 2 (MDGA2), regulate trans-synaptic adhesion between neurexins and neuroligins, impacting NLGN2 and NLGN1, respectively...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641111/structural-insights-into-modulation-of-neurexin-neuroligin-trans-synaptic-adhesion-by-mdga1-neuroligin-2-complex
#7
Jung A Kim, Doyoun Kim, Seoung Youn Won, Kyung Ah Han, Dongseok Park, Eunju Cho, Nayoung Yun, Hyun Joo An, Ji Won Um, Eunjoon Kim, Jie-Oh Lee, Jaewon Ko, Ho Min Kim
Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) bind directly to neuroligin-1 (NL1) and neuroligin-2 (NL2), thereby respectively regulating excitatory and inhibitory synapse development. However, the mechanisms by which MDGAs modulate NL activity to specify development of the two synapse types remain unclear. Here, we determined the crystal structures of human NL2/MDGA1 Ig1-3 complex, revealing their stable 2:2 arrangement with three interaction interfaces. Cell-based assays using structure-guided, site-directed MDGA1 mutants showed that all three contact patches were required for the MDGA's negative regulation of NL2-mediated synaptogenic activity...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28607166/unique-versus-redundant-functions-of-neuroligin-genes-in-shaping-excitatory-and-inhibitory-synapse-properties
#8
Soham Chanda, W Dylan Hale, Bo Zhang, Marius Wernig, Thomas C Südhof
Neuroligins are evolutionarily conserved postsynaptic cell adhesion molecules that interact with presynaptic neurexins. Neurons express multiple neuroligin isoforms that are targeted to specific synapses, but their synaptic functions and mechanistic redundancy are not completely understood. Overexpression or RNAi-mediated knockdown of neuroligins, respectively, causes a dramatic increase or decrease in synapse density, whereas genetic deletions of neuroligins impair synapse function with only minor effects on synapse numbers, raising fundamental questions about the overall physiological role of neuroligins...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28577430/posttranslational-modifications-of-neuroligins-regulate-neuronal-and-glial-signaling
#9
REVIEW
Jaehoon Jeong, Jeremiah D Paskus, Katherine W Roche
This review covers the dynamic regulation of neuroligin isoforms, focusing on posttranslational events including phosphorylation, glycosylation and activity-dependent cleavage. There is a growing literature on how phosphorylation confers an isoform-specific level of modulation affecting a variety of protein interactions. In addition, recent studies describe activity-dependent proteolytic cleavage of neuroligins, revealing a broader role for neuroligins than just synaptic 'glue'. Interesting new research implicates the cleaved extracellular fragments of neuroligins in promoting glioma...
May 31, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28515678/soluble-ectodomain-of-neuroligin-1-decreases-synaptic-activity-by-activating-metabotropic-glutamate-receptor-2
#10
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
#11
Renjun Tu, Jinjun Qian, Menglong Rui, Nana Tao, Mingkuan Sun, Yan Zhuang, Huihui Lv, Junhai Han, Moyi Li, Wei Xie
Neuroligins (Nlgs) 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 Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg 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...
June 1, 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
#12
Sandra Schilling, Annika Mehr, Susann Ludewig, Jonathan Stephan, Marius Zimmermann, Alexander August, Paul Strecker, Martin Korte, Edward H Koo, Ulrike C 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 (SAMs) due to its impact on synapse formation and synaptic plasticity. These functions are mediated by both the secreted APP ectodomain that acts as a neurotrophic factor and full-length APP forming trans-cellular dimers. Two homologs of APP exist in mammals: the APP like proteins APLP1 and APLP2, exhibiting functions that partly overlap with those of APP. Here we tested whether APLP1 and APLP2 also show features of SAMs...
May 24, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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.)
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