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https://www.readbyqxmd.com/read/28641112/molecular-mechanism-of-mdga1-regulation-of-neuroligin-2-neurexin-trans-synaptic-bridges
#1
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
#2
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-vs-redundant-functions-of-neuroligin-genes-in-shaping-excitatory-and-inhibitory-synapse-properties
#3
Soham Chanda, William D 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 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...
June 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28602954/a-versatile-genetic-tool-to-study-midline-glia-function-in-the-drosophila-cns
#4
Swati Banerjee, E Mino, Elizabeth S Fisher, Manzoor A Bhat
Neuron-glial interactions are crucial for growth, guidance and ensheathment of axons across species. In the Drosophila CNS midline, neuron-glial interactions underlie ensheathment of commissural axons by midline glial (MG) cells in a manner similar to mammalian oligodendrocytes. Although there has been some advance in the study of neuron-glial interactions and ensheathment of axons in the CNS midline, key aspects of axonal ensheathment are still not fully understood. One of the limitations has been the unavailability of MG membrane markers that could highlight the glial processes wrapping the axons...
June 8, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28515678/soluble-ectodomain-of-neuroligin-1-decreases-synaptic-activity-by-activating-metabotropic-glutamate-receptor-2
#5
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/28472659/conditional-deletion-of-all-neurexins-defines-diversity-of-essential-synaptic-organizer-functions-for-neurexins
#6
Lulu Y Chen, Man Jiang, Bo Zhang, Ozgun Gokce, Thomas C Südhof
Neurexins are recognized as key organizers of synapses that are essential for normal brain function. However, it is unclear whether neurexins are fundamental building blocks of all synapses with similar overall functions or context-dependent specifiers of synapse properties. To address this question, we produced triple cKO (conditional knockout) mice that allow ablating all neurexin expression in mice. Using neuron-specific manipulations combined with immunocytochemistry, paired recordings, and two-photon Ca(2+) imaging, we analyzed excitatory synapses formed by climbing fibers on Purkinje cells in cerebellum and inhibitory synapses formed by parvalbumin- or somatostatin-positive interneurons on pyramidal layer 5 neurons in the medial prefrontal cortex...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28461239/phred-1-is-a-divergent-neurexin-1-homolog-that-organizes-muscle-fibers-and-patterns-organs-during-regeneration
#7
Carolyn E Adler, Alejandro Sánchez Alvarado
Regeneration of body parts requires the replacement of multiple cell types. To dissect this complex process, we utilized planarian flatworms that are capable of regenerating any tissue after amputation. An RNAi screen for genes involved in regeneration of the pharynx identified a novel gene, Pharynx regeneration defective-1 (PHRED-1) as essential for normal pharynx regeneration. PHRED-1 is a predicted transmembrane protein containing EGF, Laminin G, and WD40 domains, is expressed in muscle, and has predicted homologs restricted to other lophotrochozoan species...
April 29, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28450540/aplp1-is-a-synaptic-cell-adhesion-molecule-supporting-maintenance-of-dendritic-spines-and-basal-synaptic-transmission
#8
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/28449070/in-situ-screening-for-postsynaptic-cell-adhesion-molecules-during-synapse-formation
#9
Takeshi Uemura, Tomoko Shiroshima, Asami Maeda, Misato Yasumura, Takashi Shimada, Yuko Fukata, Masaki Fukata, Tomoyuki Yoshida
Neuronal synapse formation is regulated by pre- and postsynaptic cell adhesion molecules. Presynaptic neurexins (NRXNs) and receptor protein tyrosine phosphatases (RPTPs; PTPδ, PTPσ, and LAR in mammals) can induce postsynaptic differentiation through the interaction with various postsynaptic cell adhesion molecules. Here, we developed a novel in situ screening method to identify postsynaptic membranous proteins involved in synaptogenesis. Magnetic beads coated with the extracellular domains of NRXN1β(-S4) and PTPδ-A6 variants preferentially induced excitatory postsynaptic differentiation on the beads' surface when co-cultured with cortical neurons...
April 25, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#10
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440219/correction-an-alternative-splicing-switch-shapes-neurexin-repertoires-in-principal-neurons-versus-interneurons-in-the-mouse-hippocampus
#11
Thi-Minh Nguyen, Dietmar Schreiner, Le Xiao, Lisa Traunmüller, Caroline Bornmann, Peter Scheiffele
No abstract text is available yet for this article.
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28434869/worms-on-the-spectrum-c-elegans-models-in-autism-research
#12
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/28409176/systemic-analysis-of-osteoblast-specific-dna-methylation-marks-reveals-novel-epigenetic-basis-of-osteoblast-differentiation
#13
Fangtang Yu, Hui Shen, Hong-Wen Deng
DNA methylation is an important epigenetic modification that contributes to the lineage commitment and specific functions of different cell types. In this study, we compared ENCODE-generated genome-wide DNA methylation profiles of human osteoblast with 21 other types of human cells in order to identify osteoblast-specific methylation events. For most of the cell strains, data from two isogenic replicates were included, resulting in a total of 51 DNA methylation datasets. We identified 852 significant osteoblast-specific differentially methylated CpGs (DMCs) and 295 significant differentially methylated regions (DMRs)...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28366281/neurexin-restricts-axonal-branching-in-columns-by-promoting-ephrin-clustering
#14
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
#15
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/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#16
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
May 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28320946/correction-for-sterky-et-al-carbonic-anhydrase-related-protein-ca10-is-an-evolutionarily-conserved-pan-neurexin-ligand
#17
(no author information available yet)
No abstract text is available yet for this article.
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320940/molecular-interactions-and-inhibition-of-the-staphylococcal-biofilm-forming-protein-sdrc
#18
Cécile Feuillie, Cécile Formosa-Dague, Leanne M C Hays, Ophélie Vervaeck, Sylvie Derclaye, Marian P Brennan, Timothy J Foster, Joan A Geoghegan, Yves F Dufrêne
Staphylococcus aureus forms biofilms on indwelling medical devices using a variety of cell-surface proteins. There is growing evidence that specific homophilic interactions between these proteins represent an important mechanism of cell accumulation during biofilm formation, but the underlying molecular mechanisms are still not well-understood. Here we report the direct measurement of homophilic binding forces by the serine-aspartate repeat protein SdrC and their inhibition by a peptide. Using single-cell and single-molecule force measurements, we find that SdrC is engaged in low-affinity homophilic bonds that promote cell-cell adhesion...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28298428/autoantibodies-to-synaptic-receptors-and-neuronal-cell-surface-proteins-in-autoimmune-diseases-of-the-central-nervous-system
#19
REVIEW
Josep Dalmau, Christian Geis, Francesc Graus
Investigations in the last 10 years have revealed a new category of neurological diseases mediated by antibodies against cell surface and synaptic proteins. There are currently 16 such diseases all characterized by autoantibodies against neuronal proteins involved in synaptic signaling and plasticity. In clinical practice these findings have changed the diagnostic and treatment approach to potentially lethal, but now treatable, neurological and psychiatric syndromes previously considered idiopathic or not even suspected to be immune-mediated...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28289584/mutation-analysis-of-the-nrxn1-gene-in-autism-spectrum-disorders
#20
H Onay, D Kacamak, A N Kavasoglu, B Akgun, M Yalcinli, S Kose, B Ozbaran
The aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient...
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
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