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The neurexins are a family of synaptic adhesion proteins encoded by paralogous genes that play key roles in synaptic function.
These co-occurring hits involved known disease-associated genes such as SETD5, AUTS2, and NRXN1, and were enriched for cellular and developmental processes. Accurate genetic diagnosis of complex disorders will require complete evaluation of the genetic background even after a candidate disease-associated variant is identified
Our results suggest that disruption of the CASK-neurexin interaction, not the CASK-Tbr-1 interaction, produces microcephaly and cerebellar hypoplasia.
The Nrxn1beta-LRRTM2 interface involves Ca(2+)-mediated interactions and overlaps with the Nrxn-neuroligin interface.
Dual mutations of NRXN1 and TP53 proteins are associated with different drug responses in gastric cancer.
findings did not support a major role of prominent NRXN1 gene polymorphisms in tardive dyskinesia
NRXN2 may play a part in early cortical synaptogenesis, but NRXNs could have diverse roles in development including axon guidance, and intercellular communication between proliferating cells and/or migrating neurons.
The results support the importance of exons near the 5' end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes
that alpha-Neurexin binding to alpha2delta of N-type calcium channels is a conserved mechanism for regulating synaptic transmission
NRXN1 copy number variants (deletions) were associated with increased risk of Tourette syndrome.
MDGAs regulate the formation of neuroligin-neurexin trans-synaptic bridges by sterically blocking access of neurexins to neuroligins.
In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes.
Results demonstrate that NRXN1 alternative isoform expression is temporally regulated during critical periods of human neocortical development and identify potential differential molecular contributions of NRXN1-alpha and -beta to schizophrenia and bipolar disorder
the top-ranked discordances were subsequently selected for validation by quantitative polymerase chain reaction (qPCR), from which one single ~120kb deletion in NRXN1 on chromosome 2 (bp 51017111-51136802) was validated
Atypical hand-foot-genital syndrome and developmental delay due to de novo mutations in HOXA13 and NRXN1
The rare variants in NRXN1 were significantly associated with smoking status.
NRXN1 has an affinity for binding to LRRTM2 in hippocampal synapses.
heterozygous inactivation of NRXN1 directly impairs synaptic function in human neurons.
Increasing expression of TGF-beta1 protein, decreasing expressions of Ghrelin, Neurexin, and Neuroligin proteins can induce the loss or dysfunction of ganglion cells in distal intestinal canal
Results indicate that the neurexin and neuroligin synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better understanding of the pathology of schizophrenia.
The authors find that axonal branch growth is regulated by dynamic, focal localisations of Neurexin and Neuroligin. These adhesion complexes provide stability for filopodia by a 'stick-and-grow' based mechanism wholly independent of synaptic activity.
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.
findings reveal that neurexin regulates nighttime sleep by mediating the synaptic transmission of alphabeta neurons. This study elucidates the role of synaptic transmission in sleep regulation, and might offer insights into the mechanism of sleep disturbances in patients with autism disorders.
DNrx mutants have reduced levels of Wit. Dnrx is required for proper localization and stability of Wit.
Data suggest that Nrx-1 plays critical roles in regulating synaptic terminal clustering and release of synaptic vesicles of the neuromuscular junction; Nrx-1 controls terminal clustering and release of synaptic vesicles by stimulating presynaptic actin cytoskeleton assembly; Nrx-1 functions via Scribble and Pixie to activate Rac1. (Nrx-1 = neurexin-1; Rac1 = GTP-binding protein Rac1)
DNRX was expressed preferentially in central and motor neurons in embryos, larvae and adults, but not in glial cells. DNRX was expressed in pre- and post-synaptic areas in third instar larvae neuromuscular junctions.
Dnrx1 affects synaptic plasticity and sleep.
presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality
The intracellular region of NRX interacts with N-ethylmaleimide-sensitive factor. This interaction regulates short term synaptic depression.
cooperation between Syd-1 and Nrx-1 seems to orchestrate early assembly processes between pre- and postsynaptic membranes
Together, our results provide compelling evidence for an in vivo role of neurexins in the modulation of synaptic architecture and adhesive interactions between pre- and
Neurexin-1 null mutants exhibit associative learning defect in larvad.
DNRX is essential for synaptic vesicle cycling, which plays critical roles in neurotransmission at neuromuscular junctions (NMJ).
The structure of neurexin 1alpha reveals features promoting a role as synaptic organizer
The crystal structure of the alpha-neurexin-1 extracellular region reveals a hinge point for mediating synaptic adhesion and function
structural basis for neuroligin binding
crystallographic analysis of the second LNS/LG domain from neurexin 1alpha
CA10 directly binds in a cis configuration to a conserved membrane-proximal, extracellular sequence of alpha- and beta-neurexins.
Data report that the expression of nrxn1alpha in primary cortical neuron cultures underwent activity-dependent repression and found that Ash1L binds to nrxn1alpha promoter in neurons to regulate its expression.
After pan-neurexin deletions, we observed in these synapses severe but dramatically different synaptic phenotypes that ranged from major impairments in their distribution and function (climbing-fiber synapses) to large decreases in synapse numbers (parvalbumin-positive synapses) and severe alterations in action potential-induced presynaptic Ca(2+) transients (somatostatin-positive synapses).
Findings demonstrate that the heterozygous loss of alpha-neurexin I and alpha-neurexin II in mice leads to phenotypes relevant to autism and schizophrenia
Study shows that astrocyte-secreted hevin is a trans-synaptic linker that bridges presynaptic NRX1alpha with postsynaptic NL1B. This way, hevin organizes both pre- and postsynaptic specializations and aligns them across the synapse.
Nlgn3 and Nrxn1 are differentially expressed in cerebral cortex and hippocampus which might be responsible for alterations in synaptic plasticity during agine.
This study identify distinct differences between major Nrxn variants both in surface mobility and during intracellular transport.
Mutant neurexin-1beta expression in mouse adult brain leads to core autism symptoms.
neurexin 1 interaction with multi-PDZ domain protein MUPP1
Deletions within NRXN1 found in patients may be responsible for the impairments seen in social behaviours and Nrxn1alpha knockout mice are a useful model of human neurodevelopmental disorders.
Nrxn1 and Nlgn genes that may represent an important aspect of their function at synapses in health and disease
Cross-species co-expression and protein interaction network analyses identify glycogen synthase kinase 3 beta (GSK3B) as one of the most consistent and conserved covariates of NRXN1.
Parallel fiber protrusion triggered by neurexin signaling promotes bidirectional maturation of parallel fiber-Purkinje cell synapses by positive feedback.
behavioral manifestations caused by NRXN1alpha gene mutations; gender-specific mechanisms play an important role in Nrxn1alpha-induced phenotypes.
Neurexin-1alpha is a component of the beta-cell secretory machinery and contributes to secretory granule docking, most likely through interactions with granuphilin.
Findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system.
Presenilin/gamma-secretase regulates neurexin processing at synapses
Data show that Cbln1 and Cbln2, but not Cbln4, specifically bind to neurexin 1alpha and -beta and induce synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro.
Data indicate that both NRX1alpha and NRX1beta are delivered to presynaptic terminals but show significant and different turnover rate at the membrane.
Neurexins function in the vertebrate nervous system as cell adhesion molecules and receptors. Two neurexin genes are among the largest known in human (NRXN1 and NRXN3). By using alternate promoters, splice sites and exons, predictions of hundreds or even thousands of distinct mRNAs have been made. Most transcripts use the upstream promoter and encode alpha-neurexin isoforms\; fewer transcripts are produced from the downstream promoter and encode beta-neurexin isoforms. Alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and they interact with neurexophilins. Beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. The RefSeq Project has decided to create only a few representative transcript variants of the multitude that are possible.
, drosophila neurexin
, neurexin 1
, neurexin I-alpha
, neurexin I-beta
, non-processed neurexin I-alpha
, neurexin I alpha
, neurexin 1 alpha
, neurexin 1 beta
, neurexin-1-beta isoform alpha1
, neurexin-1-beta isoform alpha2
, neurexin I-like
, alpha-latrotoxin receptor (calcium-dependent)
, neurexin Ib-alpha
, neurexin Ib-beta