scholarly journals Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 “Signalosome”

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Sylwia Owczarek ◽  
Marie Louise Bang ◽  
Vladimir Berezin
Keyword(s):  
Central Nervous System ◽  
Cell Adhesion Molecules ◽  
Synaptic Membranes ◽  
Dependent Manner ◽  
Related Protein ◽  
Synaptic Complex ◽  
The Central Nervous System ◽  
And Function ◽  
Activity Dependent ◽  
The Brain

Neurexins (NXs) and neuroligins (NLs) are cell adhesion molecules that are localized at opposite sites of synaptic membranes. They interact with each other to promote the assembly, maintenance, and function of synapses in the central nervous system. Both NX and NL are cleaved from a membrane-attached intracellular domain in an activity-dependent manner, generating the soluble ectodomain of NX or NL. Expression of theNX1andNX3genes in the brain appears to be regulated by a schizophrenia-related protein, DISC1. Here, we show that soluble ecto-NX1βcan regulate the expression of DISC1 and induce signaling downstream of DISC1. We also show that NL1 binds to a well-characterized DISC1 interaction partner, Kal-7, and this interaction can be compromised by DISC1. Our results indicate that the NX/NL synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better understanding of the pathology of schizophrenia.

CD200-, CX3CL1-, and TREM2-mediated neuron-microglia interactions and their involvements in Alzheimer’s disease

2018 ◽  
Vol 29 (8) ◽  
pp. 837-848 ◽  
Author(s):  
Lihang Zhang ◽  
Juan Xu ◽  
Jinchao Gao ◽  
Yuncheng Wu ◽  
Ming Yin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Central Nervous System ◽  
Dependent Manner ◽  
Independent Manner ◽  
Physiological Conditions ◽  
The Central Nervous System ◽  
And Function ◽  
Cluster Of Differentiation ◽  
The Brain

Abstract Neurons and microglia are two major components in the central nervous system (CNS). The interactions between them play important roles in maintaining homeostasis of the brain. In recent years, substantial studies have focused on the interactions between neurons and microglia, revealing that microglia become reactive when the interactions are pathophysiologically interfered, usually accompanying neuronal injury, which is a common feature for Alzheimer’s disease (AD). Many molecules and factors participate in these physiological and pathological processes, either in a contact-dependent or a contact-independent manner. Accumulating studies have revealed that in the CNS, cluster of differentiation-200 (CD200) and fractalkine (CX3CL1) expressed mainly on neurons and triggering receptor expressed on myeloid cells 2 (TREM2) expressed mainly on microglia. These molecules can mediate neuron-microglia interactions in a contact-dependent manner and contribute to the pathogenesis of AD. Here, we review the expression, distribution, and function of CD200, CX3CL1, and TREM2 in regulating neuron-microglia interactions under physiological conditions as well as in AD.

scholarly journals Astroglial Integrins in the Development and Regulation of Neurovascular Units

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hironobu Tanigami ◽  
Takayuki Okamoto ◽  
Yuichi Yasue ◽  
Motomu Shimaoka
Keyword(s):  
Central Nervous System ◽  
Cell Adhesion Molecules ◽  
Energy Demand ◽  
Vascular Tone ◽  
Neurovascular Unit ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
The Brain ◽  
Signaling Activity ◽  
Cerebral Vascular

In the neurovascular units of the central nervous system, astrocytes form extensive networks that physically and functionally connect the neuronal synapses and the cerebral vascular vessels. This astrocytic network is thought to be critically important for coupling neuronal signaling activity and energy demand with cerebral vascular tone and blood flow. To establish and maintain this elaborate network, astrocytes must precisely calibrate their perisynaptic and perivascular processes in order to sense and regulate neuronal and vascular activities, respectively. Integrins, a prominent family of cell-adhesion molecules that support astrocytic migration in the brain during developmental and normal adult stages, have been implicated in regulating the integrity of the blood brain barrier and the tripartite synapse to facilitate the formation of a functionally integrated neurovascular unit. This paper describes the significant roles that integrins and connexins play not only in regulating astrocyte migration during the developmental and adult stages of the neurovascular unit, but also in general health and in such diseases as hepatic encephalopathy.

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Shigetaka Yoshida
Keyword(s):  
Central Nervous System ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
The Central Nervous System ◽  
Synaptic Changes ◽  
Adhesive Molecules ◽  
High Level ◽  
Activity Dependent ◽  
The Brain

Abstract Klk8 is a tryptic serine protease with limited substrate specificity. Klk8 mRNA is expressed in many developing organs, whereas its expression is confined to limited regions, including the hippocampus, in adults. In the hippocampus, Klk8 is involved in activity-dependent synaptic changes such as long-term potentiation, which was found to be suppressed in Klk8 knockout (KO) mice. Oligodendrocytes only expressed Klk8 mRNA after injury to the central nervous system. The epidermis of the skin is one of the tissues that exhibits a high level of KLK8 expression. Klk8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis. Klk8 might thus be involved in tissue development and rearrangement.

scholarly journals Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C

2010 ◽  
Vol 189 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Chieh Hsu ◽  
Yuichi Morohashi ◽  
Shin-ichiro Yoshimura ◽  
Natalia Manrique-Hoyos ◽  
SangYong Jung ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Rab Gtpase ◽  
Multivesicular Bodies ◽  
Dependent Manner ◽  
Intracellular Accumulation ◽  
Gtpase Activating Proteins ◽  
The Central Nervous System ◽  
And Function ◽  
Endosomal Vesicles ◽  
Activity Dependent

Oligodendrocytes secrete vesicles into the extracellular space, where they might play a role in neuron–glia communication. These exosomes are small vesicles with a diameter of 50–100 nm that are formed within multivesicular bodies and are released after fusion with the plasma membrane. The intracellular pathways that generate exosomes are poorly defined. Because Rab family guanosine triphosphatases (GTPases) together with their regulators are important membrane trafficking organizers, we investigated which Rab GTPase-activating proteins interfere with exosome release. We find that TBC1D10A–C regulate exosome secretion in a catalytic activity–dependent manner. We show that Rab35 is the target of TBC1D10A–C and that the inhibition of Rab35 function leads to intracellular accumulation of endosomal vesicles and impairs exosome secretion. Rab35 localizes to the surface of oligodendroglia in a GTP-dependent manner, where it increases the density of vesicles, suggesting a function in docking or tethering. These findings provide a basis for understanding the biogenesis and function of exosomes in the central nervous system.

scholarly journals Repression of lysosomal transcription factors Tfeb and Tfe3 is essential for the development and function of microglia

2020 ◽  
Author(s):  
Harini Iyer ◽  
Kimberle Shen ◽  
Ana M. Meireles ◽  
William S. Talbot
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gtpase Activating Protein ◽  
Phagocytic Cells ◽  
Lysosomal Activity ◽  
Regulatory Circuit ◽  
The Central Nervous System ◽  
And Function ◽  
The Brain ◽  
Macrophage Lineage

SUMMARYAs the primary phagocytic cells of the central nervous system, microglia exquisitely regulate their lysosomal activity to facilitate brain development and homeostasis. However, mechanisms that coordinate lysosomal activity with microglia development, migration, and function remain unclear. Here we show that embryonic macrophages require the lysosomal GTPase RagA and the GTPase-activating protein Folliculin (Flcn) for colonization of the brain. Mutants lacking RagA and Flcn have nearly identical phenotypes, suggesting that RagA and Flcn act in concert in developing microglia. Furthermore, we demonstrate that RagA and Flcn repress the key lysosomal transcription factor Tfeb, and its homologs Tfe3a and Tfe3b, in macrophages. Accordingly, defects in rraga mutants can be restored by simultaneous mutations in tfeb, tfe3a, and tfe3b, and overexpression of tfe3b in the macrophage lineage recapitulates the major defects observed in rraga and flcn mutants. Collectively, our data define a lysosomal regulatory circuit that is essential for early development of microglia.

Abstract 245: Intravenously Injected Human Apolipoprotein A-I Rapidly Enters the Central Nervous System via the Choroid Plexus in Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Sophie Stukas ◽  
Jerome Robert ◽  
Michael Lee ◽  
Iva Kulic ◽  
Nicole DeValle ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Choroid Plexus ◽  
Lipoprotein Metabolism ◽  
High Density Lipoproteins ◽  
Dependent Manner ◽  
Apo E ◽  
The Central Nervous System ◽  
The Brain

Background: Lipoprotein metabolism in the brain is based on particles that resemble high-density lipoproteins (HDL) that use apolipoprotein (apo) E as opposed to apoA-I as their primary protein component. Although apoA-I is not synthesized by astrocytes or microglia, which secrete apoE, it is abundant in cerebrospinal fluid (CSF) and is readily detectable in brain tissue lysates.However, the mechanisms by which plasma apoA-I enters and is metabolized within the central nervous system (CNS) are unknown. Methods and Results: Western blot analysis shows that steady state levels of endogenous apoA-I in CSF and brain are approximately 0.01% and 10-15% of its levels in plasma and liver, respectively. Recombinant, fluorescently tagged, lipid-free human (h) apoA-I injected into the tail vein of wild-type mice localizes to the choroid plexus within 0.5h and accumulates in a saturable, dose-dependent manner in brain. hApoA-I accumulates in the brain for up to 2h, after which it is turned over with a half life of ~133 minutes, 3 times longer than the relatively quick turnover 40-45 minutes found in plasma, liver, and kidney. In vitro, hApoA-I is taken up and actively transported across confluent monolayers of primary human choroid epithelial cells. Conclusions: Following intravenous injection, hApoA-I rapidly and strongly localizes to the choroid plexus, suggesting it gains access to the CNS primarily via the blood CSF barrier. Further, apoA-I found in the CNS of mice is exclusively derived from the circulation as apoA-I mRNA is not detectable in murine brain. These results suggest that apoA-I based HDL may primarily play a role in CSF lipoprotein metabolism in addition to potentially impacting cerebrovasculature health and function from the lumen of the vessel.

scholarly journals Tumors of the Central Nervous System: An Update

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2507
Author(s):  
Carla Mucignat-Caretta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Structure ◽  
Cell Types ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
The Central Nervous System ◽  
And Function ◽  
Different Cell Types ◽  
The Brain

The brain may be affected by a variety of tumors of different grade, which originate from different cell types at distinct locations, thus impacting on the brain structure and function [...]

scholarly journals A Window into the Heterogeneity of Human Cerebrospinal Fluid AβPeptides

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Roberta Ghidoni ◽  
Anna Paterlini ◽  
Valentina Albertini ◽  
Elena Stoppani ◽  
Giuliano Binetti ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Basic Research ◽  
Brain Diseases ◽  
Human Cerebrospinal Fluid ◽  
Communication Modes ◽  
The Central Nervous System ◽  
And Function ◽  
The Brain ◽  
Obvious Source

The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (Aβ) peptides leading to the formation of neurotoxic brain Aβassemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF Aβpeptides. Specifically, we focused our attention on the heterogeneity of the CSF Aβworld discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating Aβassemblies, and (3) communication modes for Aβpeptides and their microenvironment targets. Finally, we suggest that Aβpeptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

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