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https://www.readbyqxmd.com/read/29784826/deletion-of-lrrtm1-and-lrrtm2-in-adult-mice-impairs-basal-ampa-receptor-transmission-and-ltp-in-hippocampal-ca1-pyramidal-neurons
#1
Mehdi Bhouri, Wade Morishita, Paul Temkin, Debanjan Goswami, Hiroshi Kawabe, Nils Brose, Thomas C Südhof, Ann Marie Craig, Tabrez J Siddiqui, Robert Malenka
Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse ( LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784783/postsynaptic-%C3%AE-1-glutamate-receptor-assembles-and-maintains-hippocampal-synapses-via-cbln2-and-neurexin
#2
Wucheng Tao, Javier Díaz-Alonso, Nengyin Sheng, Roger A Nicoll
The δ1 glutamate receptor (GluD1) was cloned decades ago and is widely expressed in many regions of the brain. However, its functional roles in these brain circuits remain unclear. Here, we find that GluD1 is required for both excitatory synapse formation and maintenance in the hippocampus. The action of GluD1 is absent in the Cbln2 knockout mouse. Furthermore, the GluD1 actions require the presence of presynaptic neurexin 1β carrying the splice site 4 insert (+S4). Together, our findings demonstrate that hippocampal synapse assembly and maintenance require a tripartite molecular complex in which the ligand Cbln2 binds with presynaptic neurexin 1β (+S4) and postsynaptic GluD1...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29782851/glycosylation-of-cblns-attenuates-their-receptor-binding
#3
Yongqi Rong, Parmil K Bansal, Peng Wei, Hong Guo, Kristen Correia, Jennifer Parris, James I Morgan
Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2. Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns. Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding. Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding...
May 18, 2018: Brain Research
https://www.readbyqxmd.com/read/29691328/genetic-ablation-of-all-cerebellins-reveals-synapse-organizer-functions-in-multiple-regions-throughout-the-brain
#4
Erica Seigneur, Thomas C Südhof
Cerebellins are synaptic organizer molecules that bind to presynaptic neurexins and postsynaptic receptors. Cerebellins are well studied in cerebellum, but three of the four cerebellins (Cbln1, Cbln2, and Cbln4) are also broadly expressed outside of the cerebellum, suggesting that they perform general functions throughout the brain. Here we generated male and female single, double, and triple constitutive KO mice of Cbln1, Cbln2, and Cbln4. We found that all constitutive cerebellin-deficient mice are viable and fertile, suggesting that cerebellins are not essential for survival...
April 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29681532/a-missense-variant-at-the-nrxn3-locus-enhances-empathy-fear-in-the-mouse
#5
Sehoon Keum, Arie Kim, Jae Jin Shin, Jong-Hyun Kim, Joomin Park, Hee-Sup Shin
Empathy is crucial for our emotional experience and social interactions, and its abnormalities manifest in various psychiatric disorders. Observational fear is a useful behavioral paradigm for assessing affective empathy in rodents. However, specific genes that regulate observational fear remain unknown. Here we showed that 129S1/SvImJ mice carrying a unique missense variant in neurexin 3 (Nrxn3) exhibited a profound and selective enhancement in observational fear. Using the CRISPR/Cas9 system, the arginine-to-tryptophan (R498W) change in Nrxn3 was confirmed to be the causative variant...
April 17, 2018: Neuron
https://www.readbyqxmd.com/read/29622757/significance-of-neurexin-and-neuroligin-polymorphisms-in-regulating-risk-of-hirschsprung-s-disease
#6
Yanhong Li, Hui Liu, Yubin Dong
By performing a basic case-control study among a Chinese population, the aims of this study were to explore if single nucleotide polymorphisms (SNPs) within neurexin and neuroligin were associated with susceptibility to Hirschsprung's disease (HD). Eleven SNPs within neurexin and neuroligin were selected in this basic case-control study, and this study recruited 210 children with HD and 187 healthy children. The t-test and Χ2 test were used to find the difference between case and control in their clinical variables...
April 4, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29593501/chronic-stress-reduces-nectin-1-mrna-levels-and-disrupts-dendritic-spine-plasticity-in-the-adult-mouse-perirhinal-cortex
#7
Qian Gong, Yun-Ai Su, Chen Wu, Tian-Mei Si, Jan M Deussing, Mathias V Schmidt, Xiao-Dong Wang
In adulthood, chronic exposure to stressful experiences disrupts synaptic plasticity and cognitive function. Previous studies have shown that perirhinal cortex-dependent object recognition memory is impaired by chronic stress. However, the stress effects on molecular expression and structural plasticity in the perirhinal cortex remain unclear. In this study, we applied the chronic social defeat stress (CSDS) paradigm and measured the mRNA levels of nectin-1, nectin-3 and neurexin-1, three synaptic cell adhesion molecules (CAMs) implicated in the adverse stress effects, in the perirhinal cortex of wild-type (WT) and conditional forebrain corticotropin-releasing hormone receptor 1 conditional knockout (CRHR1-CKO) mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29559501/synaptogenesis-is-modulated-by-heparan-sulfate-in-caenorhabditis-elegans
#8
María Lázaro-Peña, Carlos Díaz-Balzac, Hannes Bülow, Scott Emmons
The nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in C. elegans It is composed of sequential steps that are governed by more than 3,000 chemical connections. Here we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. HS, sulfated in position 3 by the HS modification enzyme HST-3.1 / HS 3- O -sulfotransferase and attached to the HSPG glypicans LON-2/glypican and GPN-1/glypican, functions cell-autonomously and non-autonomously for response to hermaphrodite contact during mating...
March 20, 2018: Genetics
https://www.readbyqxmd.com/read/29537369/neurexin-neuroligin-1-regulates-synaptic-morphology-and-functions-via-the-wave-regulatory-complex-in-drosophila-neuromuscular-junction
#9
Guanglin Xing, Moyi Li, Yichen Sun, Menglong Rui, Yan Zhuang, Huihui Lv, Junhai Han, Zhengping Jia, Wei Xie
Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of neuroligin functions remain unclear. We found that Drosophila Neuroligin 1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence...
March 14, 2018: ELife
https://www.readbyqxmd.com/read/29513122/treatment-of-secondary-brain-injury-by-perturbing-postsynaptic-density-protein-95-nmda-receptor-interaction-after-intracerebral-hemorrhage-in-rats
#10
Zhifeng Wang, Zhouqing Chen, Junjie Yang, Ziying Yang, Jia Yin, Xiaochun Duan, Haitao Shen, Haiying Li, Zhong Wang, Gang Chen
Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29504935/neurexin-and-neuroligin-based-adhesion-complexes-drive-axonal-arborisation-growth-independent-of-synaptic-activity
#11
William D Constance, Amrita Mukherjee, Yvette E Fisher, Sinziana Pop, Eric Blanc, Yusuke Toyama, Darren W Williams
Building arborisations of the right size and shape is fundamental for neural network function. Live imaging in vertebrate brains strongly suggests that nascent synapses are critical for branch growth during development. The molecular mechanisms underlying this are largely unknown. Here we present a novel system in Drosophila for studying the development of complex arborisations live, in vivo during metamorphosis. In growing arborisations we see branch dynamics and localisations of presynaptic proteins very similar to the 'synaptotropic growth' described in fish/frogs...
March 5, 2018: ELife
https://www.readbyqxmd.com/read/29449804/an-early-sensitive-period-induces-long-lasting-plasticity-in-the-honeybee-nervous-system
#12
Juan P Grosso, Jesica A Barneto, Rodrigo A Velarde, Eduardo A Pagano, Jorge A Zavala, Walter M Farina
The effect of early experiences on the brain during a sensitive period exerts a long-lasting influence on the mature individual. Despite behavioral and neural plasticity caused by early experiences having been reported in the honeybee Apis mellifera , the presence of a sensitive period in which associative experiences lead to pronounced modifications in the adult nervous system is still unclear. Laboratory-reared bees were fed with scented food within specific temporal windows and were assessed for memory retention, in the regulation of gene expression related to the synaptic formation and in the olfactory perception of their antennae at 17 days of age...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29426960/two-microcephaly-associated-novel-missense-mutations-in-cask-specifically-disrupt-the-cask-neurexin-interaction
#13
Leslie E W LaConte, Vrushali Chavan, Abdallah F Elias, Cynthia Hudson, Corbin Schwanke, Katie Styren, Jonathan Shoof, Fernando Kok, Sarika Srivastava, Konark Mukherjee
Deletion and truncation mutations in the X-linked gene CASK are associated with severe intellectual disability (ID), microcephaly and pontine and cerebellar hypoplasia in girls (MICPCH). The molecular origin of CASK-linked MICPCH is presumed to be due to disruption of the CASK-Tbr-1 interaction. This hypothesis, however, has not been directly tested. Missense variants in CASK are typically asymptomatic in girls. We report three severely affected girls with heterozygous CASK missense mutations (M519T (2), G659D (1)) who exhibit ID, microcephaly, and hindbrain hypoplasia...
March 2018: Human Genetics
https://www.readbyqxmd.com/read/29406991/a-new-etiologic-model-for-alzheimers-disease
#14
Kathryn A Schiel
This etiologic model proposes that Alzheimers Disease (AD) arises when an unusually rapid increase in ventricle volume triggers axon stretch that culminates in the physical separation of trans-synaptic proteins. As a result, these proteins, such as neurexin, neuroligin, N-Cadherin and Amyloid Precursor Protein (APP), experience a change in the configuration of their cytoplasmic tail, so that instead of transmitting signals to create and maintain synaptic structure they activate enzymes, and generate molecules, that stimulate neurite growth; for example, the transformation of the N-Cadherin tail dissolves its complex with presenilin and β-catenin triggering activation of glycogen synthase kinase 3 beta (GSK3β) and cytoskeletal disruption...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29370833/synaptic-proteins-in-csf-as-potential-novel-biomarkers-for-prognosis-in-prodromal-alzheimer-s-disease
#15
Flora H Duits, Gunnar Brinkmalm, Charlotte E Teunissen, Ann Brinkmalm, Philip Scheltens, Wiesje M Van der Flier, Henrik Zetterberg, Kaj Blennow
BACKGROUND: We investigated whether a panel of 12 potential novel biomarkers consisting of proteins involved in synapse functioning and immunity would be able to distinguish patients with Alzheimer's disease (AD) and patients with mild cognitive impairment (MCI) from control subjects. METHODS: We included 40 control subjects, 40 subjects with MCI, and 40 subjects with AD from the Amsterdam Dementia Cohort who were matched for age and sex (age 65 ± 5 years, 19 [48%] women)...
January 15, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29323291/neurexin-controls-plasticity-of-a-mature-sexually-dimorphic-neuron
#16
Michael P Hart, Oliver Hobert
During development and adulthood, brain plasticity is evident at several levels, from synaptic structure and function to the outgrowth of dendrites and axons. Whether and how sex impinges on neuronal plasticity is poorly understood. Here we show that the sex-shared GABA (γ-aminobutyric acid)-releasing DVB neuron in Caenorhabditis elegans displays experience-dependent and sexually dimorphic morphological plasticity, characterized by the stochastic and dynamic addition of multiple neurites in adult males. These added neurites enable synaptic rewiring of the DVB neuron and instruct a functional switch of the neuron that directly modifies a step of male mating behaviour...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29281813/loss-of-synapse-repressor-mdga1-enhances-perisomatic-inhibition-confers-resistance-to-network-excitation-and-impairs-cognitive-function
#17
Steven A Connor, Ina Ammendrup-Johnsen, Yasushi Kishimoto, Parisa Karimi Tari, Vedrana Cvetkovska, Takashi Harada, Daiki Ojima, Tohru Yamamoto, Yu Tian Wang, Ann Marie Craig
Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29229705/proteolytic-processing-of-neurexins-by-presenilins-sustains-synaptic-vesicle-release
#18
Emilia Servián-Morilla, Estefanía Robles-Lanuza, Ana C Sánchez-Hidalgo, Rafael J Camacho-Garcia, Juan A Paez-Gomez, Fabiola Mavillard, Carlos A Saura, Amalia Martinez-Mir, Francisco G Scholl
Proteolytic processing of synaptic adhesion components can accommodate the function of synapses to activity-dependent changes. The adhesion system formed by neurexins (Nrxns) and neuroligins (Nlgns) bidirectionally orchestrate the function of presynaptic and postsynaptic terminals. Previous studies have shown that presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheimer's disease, clear from glutamatergic terminals the accumulation of Nrxn C-terminal fragments (Nrxn-CTF) generated by ectodomain shedding...
January 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29221905/neurexins-and-neuropsychiatric-disorders
#19
REVIEW
Enas Kasem, Taiga Kurihara, Katsuhiko Tabuchi
Neurexins are a family of presynaptic single-pass transmembrane proteins that act as synaptic organizers in mammals. The neurexins consist of three genes (NRXN1, NRXN2, and NRXN3), each of which produces a longer α- and shorter β-form. Genomic alterations in NRXN genes have been identified in a wide variety of neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, intellectual disability (ID), and addiction. Remarkably, a bi-allelic deficiency of NRXN1 was recently linked to Pitt-Hopkins syndrome...
February 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29217522/-drosophila-syd-1-has-rhogap-activity-that-is-required-for-presynaptic-clustering-of-bruchpilot-elks-but-not-neurexin-1
#20
Michael A Spinner, David A Walla, Tory G Herman
Syd-1 proteins are required for presynaptic development in worm, fly, and mouse. Syd-1 proteins in all three species contain a Rho GTPase activating protein (GAP)-like domain of unclear significance: invertebrate Syd-1s are thought to lack GAP activity, and mouse mSYD1A has GAP activity that is thought to be dispensable for its function. Here, we show that Drosophila melanogaster Syd-1 can interact with all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development, fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly...
February 2018: Genetics
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