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https://www.readbyqxmd.com/read/28714144/cerebellins-are-differentially-expressed-in-selective-subsets-of-neurons-throughout-the-brain
#1
Erica Seigneur, Thomas C Südhof
Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer' (DCC), and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion...
July 16, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28713908/comparison-of-gene-expression-profiles-between-dental-pulp-and-periodontal-ligament-tissues-in-humans
#2
Ai-Xiu Gong, Jing-Han Zhang, Jing Li, Jun Wu, Lin Wang, Deng-Shun Miao
There are anatomical and functional differences between human dental pulp (DP) and periodontal ligament (PDL). However, the molecular biological differences and function of these tissues are poorly understood. In the present study, we employed a cDNA microarray array to screen for differentially expressed genes (DEGs) between human DP and PDL tissues, and used the online software WebGestalt to perform the functional analysis of the DEGs. In addition, the STRING database and KEGG pathway analysis were applied for interaction network and pathway analysis of the DEGs...
July 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28710284/the-neuronal-protein-neurexin-directly-interacts-with-the-scribble-pix-complex-to-stimulate-f-actin-assembly-for-synaptic-vesicle-clustering
#3
Menglong Rui, Jinjun Qian, Lijuan Liu, Yihan Cai, Huihui Lv, Junhai Han, Zhengping Jia, Wei Xie
Synaptic vesicles (SVs) form distinct pools at synaptic terminals, and this well-regulated separation is necessary for normal neuro-transmission. However, how SV cluster in particular synaptic compartments to maintain normal neurotransmitter release remains a mystery. The presynaptic protein Neurexin (NRX) plays a significant role in synaptic architecture and function, and some evidences suggest that NRX is associated with neurological disorders, including autism spectrum disorders. However, the role of NRX in SV clustering is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28695613/ngl-3-induced-presynaptic-differentiation-of-hippocampal-neurons-in-an-afadin-dependent-nectin-1-independent-manner
#4
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
#5
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/28643105/differential-role-of-gabaa-receptors-and-neuroligin-2-for-perisomatic-gabaergic-synapse-formation-in-the-hippocampus
#6
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
#7
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
#8
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
#9
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/28602954/a-versatile-genetic-tool-to-study-midline-glia-function-in-the-drosophila-cns
#10
Swati Banerjee, Rosa 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 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28515678/soluble-ectodomain-of-neuroligin-1-decreases-synaptic-activity-by-activating-metabotropic-glutamate-receptor-2
#11
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
#12
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
#13
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...
July 1, 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
#14
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/28449070/in-situ-screening-for-postsynaptic-cell-adhesion-molecules-during-synapse-formation
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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