scholarly journals Astrocyte-Synapse Structural Plasticity

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Yann Bernardinelli ◽  
Dominique Muller ◽  
Irina Nikonenko
Keyword(s):  
Close Association ◽  
Structural Plasticity ◽  
Fine Tuning ◽  
Glutamatergic Synapses ◽  
Synaptic Structure ◽  
Synaptic Functions ◽  
And Function ◽  
Bidirectional Interactions ◽  
Synaptic Level

The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the environment in which a synapse is embedded. Glial cells constitute an important part of this environment and participate in several aspects of synaptic functions. Among the glial cell family, the roles played by astrocytes at the synaptic level are particularly important, ranging from the trophic support to the fine-tuning of transmission. Astrocytic structures are frequently observed in close association with glutamatergic synapses, providing a morphological entity for bidirectional interactions with synapses. Experimental evidence indicates that astrocytes sense neuronal activity by elevating their intracellular calcium in response to neurotransmitters and may communicate with neurons. The precise role of astrocytes in regulating synaptic properties, function, and plasticity remains however a subject of intense debate and many aspects of their interactions with neurons remain to be investigated. A particularly intriguing aspect is their ability to rapidly restructure their processes and modify their coverage of the synaptic elements. The present review summarizes some of these findings with a particular focus on the mechanisms driving this form of structural plasticity and its possible impact on synaptic structure and function.

scholarly journals Arhgap22 Disruption Leads to RAC1 Hyperactivity Affecting Hippocampal Glutamatergic Synapses and Cognition in Mice

2021 ◽  
Author(s):  
Anna Longatti ◽  
Luisa Ponzoni ◽  
Edoardo Moretto ◽  
Giorgia Giansante ◽  
Norma Lattuada ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Synapse Formation ◽  
Actin Dynamics ◽  
Spine Density ◽  
Glutamatergic Synapses ◽  
Synaptic Structure ◽  
Knockout Animal ◽  
Rac1 Activity ◽  
And Function

AbstractRho GTPases are a class of G-proteins involved in several aspects of cellular biology, including the regulation of actin cytoskeleton. The most studied members of this family are RHOA and RAC1 that act in concert to regulate actin dynamics. Recently, Rho GTPases gained much attention as synaptic regulators in the mammalian central nervous system (CNS). In this context, ARHGAP22 protein has been previously shown to specifically inhibit RAC1 activity thus standing as critical cytoskeleton regulator in cancer cell models; however, whether this function is maintained in neurons in the CNS is unknown. Here, we generated a knockout animal model for arhgap22 and provided evidence of its role in the hippocampus. Specifically, we found that ARHGAP22 absence leads to RAC1 hyperactivity and to an increase in dendritic spine density with defects in synaptic structure, molecular composition, and plasticity. Furthermore, arhgap22 silencing causes impairment in cognition and a reduction in anxiety-like behavior in mice. We also found that inhibiting RAC1 restored synaptic plasticity in ARHGAP22 KO mice. All together, these results shed light on the specific role of ARHGAP22 in hippocampal excitatory synapse formation and function as well as in learning and memory behaviors.

scholarly journals Correct CYFIP1 dosage is essential for synaptic inhibition and the excitatory/inhibitory balance.

2018 ◽  
Author(s):  
Elizabeth C Davenport ◽  
Blanka Szulc ◽  
James Drew ◽  
James Taylor ◽  
Toby Morgan ◽  
...  
Keyword(s):  
Opposite Effect ◽  
Copy Number Variations ◽  
Conditional Knockout ◽  
Inhibitory Synapses ◽  
Synaptic Inhibition ◽  
Postsynaptic Currents ◽  
Synaptic Structure ◽  
And Function

Altered excitatory/inhibitory balance is implicated in neuropsychiatric disorders but the genetic aetiology of this is still poorly understood. Copy number variations in CYFIP1 are associated with autism, schizophrenia and intellectual disability but the role of CYFIP1 in regulating synaptic inhibition or excitatory/inhibitory balance remains unclear. We show, CYFIP1, and its paralogue CYFIP2, are enriched at inhibitory postsynaptic sites. While upregulation of CYFIP1 or CYFIP2 increased excitatory synapse number and the frequency of miniature excitatory postsynaptic currents (mEPSCs), it had the opposite effect at inhibitory synapses, decreasing their size and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Contrary to CYFIP1 upregulation, its loss in vivo, upon conditional knockout in neocortical principal cells, increased expression of postsynaptic GABA A receptor β2/3-subunits and neuroligin 3 and enhanced synaptic inhibition. Thus, CYFIP1 dosage can bi-directionally impact inhibitory synaptic structure and function, potentially leading to altered excitatory/inhibitory balance and circuit dysfunction in CYFIP1-associated neurodevelopmental disorders.

scholarly journals Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells

2015 ◽  
Vol 112 (30) ◽  
pp. 9394-9399 ◽  
Author(s):  
Chi-Keung Wan ◽  
Allison B. Andraski ◽  
Rosanne Spolski ◽  
Peng Li ◽  
Majid Kazemian ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Lymphocytic Choriomeningitis ◽  
Fine Tuning ◽  
Type I ◽  
Rna Seq ◽  
Ifn Γ ◽  
And Function

IL-21 is a type I cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signaling in CD4+ T cells. IL-21 induced STAT1 phosphorylation, and this was augmented in Stat3-deficient CD4+ T cells. RNA-Seq analysis of CD4+ T cells from Stat1- and Stat3-deficient mice revealed that both STAT1 and STAT3 are critical for IL-21–mediated gene regulation. Expression of some genes, including Tbx21 and Ifng, was differentially regulated by STAT1 and STAT3. Moreover, opposing actions of STAT1 and STAT3 on IFN-γ expression in CD4+ T cells were demonstrated in vivo during chronic lymphocytic choriomeningitis infection. Finally, IL-21–mediated induction of STAT1 phosphorylation, as well as IFNG and TBX21 expression, were higher in CD4+ T cells from patients with autosomal dominant hyper-IgE syndrome, which is caused by STAT3 deficiency, as well as in cells from STAT1 gain-of-function patients. These data indicate an interplay between STAT1 and STAT3 in fine-tuning IL-21 actions.

scholarly journals Dynamic mRNA modifications: An emerging layer of gene regulation

2015 ◽  
Vol 37 (2) ◽  
pp. 14-18 ◽  
Author(s):  
Adrian Whitehouse
Keyword(s):  
Gene Regulation ◽  
Messenger Rna ◽  
Fine Tuning ◽  
Minor Role ◽  
Small Nuclear Rna ◽  
Non Coding Rna ◽  
A Minor ◽  
And Function ◽  
Long Non Coding Rna

More than 100 different types of chemical modifications are found in cellular RNAs, including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA) and small nuclear RNA (snRNA). Internal modifications of mRNA were first observed in the 1970s, but, until recently, the role of these mRNA modifications has been a largely neglected field. A long-standing view was that mRNA modifications were static and unalterable, having a minor role in fine-tuning the structure and function of mRNAs. However, recent exciting discoveries now suggest that certain mRNA modifications are dynamic and, in some cases, reversible. Therefore they may have critical regulatory roles in gene expression, analogous to those which dynamically regulate DNA and protein modifications. As such, understanding the scope and mechanisms of these dynamic mRNA modifications represents an emerging layer of gene regulation at the RNA level, termed epitranscriptomics or RNA epigenetics.

scholarly journals The Role of Vitamin D in Cognitive Disorders in Older Adults

US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 41 ◽  
Author(s):  
Jake Gold ◽  
Abdullah Shoaib ◽  
Gopinath Gorthy ◽  
George T Grossberg
Keyword(s):  
Older Adults ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Cognitive Disorders ◽  
Normal Brain ◽  
Brain Functions ◽  
Synaptic Structure ◽  
Calcium Phosphorus ◽  
And Function

The physiological effects of vitamin D on calcium/phosphorus metabolism have been well studied since its discovery in the early 20th century. With recent advances in cellular and molecular biology, its role in maintaining normal brain functions and the protection of neurons via maintenance of cellular homeostasis, immune regulation, modulation of synaptic structure and function are more clearly known. Recently, its deficiency is increasingly implicated in major neurocognitive disorders including Alzheimer’s disease, Parkinson’s disease, and vascular dementia. Older adults are particularly vulnerable not only because vitamin D deficiency becomes more prevalent with aging, but they also are often complicated with other comorbid illnesses. This article reviews the role of vitamin D in maintaining normal brain functions, and implications for vitamin D deficiency in cognitive disorders.

scholarly journals Non-apoptotic function of caspase-3 in morphogenesis of epithelial tubes of Drosophila renal system

2020 ◽  
Author(s):  
Shainy Ojha ◽  
Madhu G. Tapadia
Keyword(s):  
Caspase 3 ◽  
Stellate Cells ◽  
Probable Mechanism ◽  
Malpighian Tubules ◽  
Fine Tuning ◽  
Convergent Extension ◽  
Cytoskeleton Organization ◽  
Cell Mobility ◽  
And Function

AbstractCells trigger apoptosis to eliminate themselves from the system, when tissue needs to be sculptured or they detect any abnormality within them, thus preventing irreparable damage to the host. Drosophila Malpighian tubules express apoptotic proteins, without succumbing to cell death. Here we present evidence to show apoptosis independent role of executioner caspase, Drice, for precise architecture and function of Malpighian tubules. Drice is required for precise cytoskeleton organization and convergent extension, failing which the morphology, size, cellular number and arrangement gets affected. Acquisition of star shape of stellate cells in adult Malpighian tubules requires Drice. We demonstrate that Drice regulates expression of Rho1GTPase and localization of polarity proteins. Our study shows a probable mechanism by which Drice governs tubulogenesis via Rho1GTPase mediated coordinated organization of actin cytoskeleton and membrane stablisation. Furthermore, defective morphology of tubules leads to abnormal osmoregulation and excretory functions. Collectively our findings suggest a possible non-apoptotic function of caspase-3 in the fine tuning of cell mobility during tubule development and our results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans.

Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

1986 ◽  
Vol 44 ◽  
pp. 208-209
Author(s):  
Grace C.H. Yang
Keyword(s):  
Chick Embryo ◽  
Extracellular Space ◽  
Fibroblast Cell ◽  
Collagen Fibrils ◽  
Electron Microscopic ◽  
Voltage Electron ◽  
Scanning Electron Microscopic Study ◽  
Microscopic Studies ◽  
And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

Role of the Cilia Membrane in Control of Microtubule Sliding

1980 ◽  
Vol 38 ◽  
pp. 612-615
Author(s):  
Edna S. Kaneshiro
Keyword(s):  
Control Mechanism ◽  
Beat Frequency ◽  
Surface Membrane ◽  
Ciliary Membrane ◽  
Ciliary Beating ◽  
Ciliary Reversal ◽  
Voltage Dependent ◽  
Reversal Mechanism ◽  
And Function

It is currently believed that ciliary beating results from microtubule sliding which is restricted in regions to cause bending. Cilia beat can be modified to bring about changes in beat frequency, cessation of beat and reversal in beat direction. In ciliated protozoans these modifications which determine swimming behavior have been shown to be related to intracellular (intraciliary) Ca2+ concentrations. The Ca2+ levels are in turn governed by the surface ciliary membrane which exhibits increased Ca2+ conductance (permeability) in response to depolarization. Mutants with altered behaviors have been isolated. Pawn mutants fail to exhibit reversal of the effective stroke of ciliary beat and therefore cannot swim backward. They lack the increased inward Ca2+ current in response to depolarizing stimuli. Both normal and pawn Paramecium made leaky to Ca2+ by Triton extrac¬tion of the surface membrane exhibit backward swimming only in reactivating solutions containing greater than IO-6 M Ca2+ Thus in pawns the ciliary reversal mechanism itself is left operational and only the control mechanism at the membrane is affected. The topographic location of voltage-dependent Ca2+ channels has been identified as a component of the ciliary mem¬brane since the inward Ca2+ conductance response is eliminated by deciliation and the return of the response occurs during cilia regeneration. Since the ciliary membrane has been impli¬cated in the control of Ca2+ levels in the cilium and therefore is the site of at least one kind of control of microtubule sliding, we have focused our attention on understanding the structure and function of the membrane.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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