Differential Control of Thrombospondin over Synaptic Glycine and AMPA Receptors in Spinal Cord Neurons

Hennekinne, Laetitia; Colasse, Sabrina; Triller, Antoine; Renner, Marianne

doi:10.1523/jneurosci.5247-12.2013

Cited by 48 publications

(44 citation statements)

References 35 publications

(7 reference statements)

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“…These include factors that increase synaptic AMPARs (glypican 4 and −6, Gpc4/6; tumor necrosis factor [TNF]-α), decrease synaptic AMPARs (SPARC; TSP), stabilize surface AMPARs (chondroitin sulfate proteoglycans [CSPGs]), and increase synaptic NMDA glutamate receptors (NMDARs) (activity-dependent neurotrophic factor [ADNF]) (Blondel et al 2000; Beattie et al 2002; Jones et al 2011; Pyka et al 2011; Allen et al 2012; Hennekinne et al 2013). …”

Section: Astrocytes Regulate Synaptic Functionmentioning

confidence: 99%

“…Secretion of SPARC from astrocytes is regulated by neuronal activity, being increased when neuronal activity increases, suggesting that SPARC acts to limit neuronal overexcitation from occurring by reducing synaptic AMPAR levels. TSP has differential effects over AMPARs and glycine receptors in mature cultures of spinal cord neurons in which synapses have already formed (Hennekinne et al 2013). TSP increases synaptic glycine receptors and decreases synaptic AMPARs, so decreasing neuronal excitability.…”

Section: Astrocytes Regulate Synaptic Functionmentioning

confidence: 99%

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Astrocytes Control Synapse Formation, Function, and Elimination

Chung

Allen

Eroğlu

2015

Cold Spring Harb Perspect Biol

609

514

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Astrocytes, through their close associations with synapses, can monitor and alter synaptic function, thus actively controlling synaptic transmission in the adult brain. Besides their important role at adult synapses, in the last three decades a number of critical findings have highlighted the importance of astrocytes in the establishment of synaptic connectivity in the developing brain. In this article, we will review the key findings on astrocytic control of synapse formation, function, and elimination. First, we will summarize our current structural and functional understanding of astrocytes at the synapse. Then, we will discuss the cellular and molecular mechanisms through which developing and mature astrocytes instruct the formation, maturation, and refinement of synapses. Our aim is to provide an overview of astrocytes as important players in the establishment of a functional nervous system.

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Section: Astrocytes Regulate Synaptic Functionmentioning

confidence: 99%

Section: Astrocytes Regulate Synaptic Functionmentioning

confidence: 99%

Astrocytes Control Synapse Formation, Function, and Elimination

Chung

Allen

Eroğlu

2015

Cold Spring Harb Perspect Biol

609

514

View full text Add to dashboard Cite

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“…The identification of several motor proteins as gephyrin interactors also raised the possibility that a non-clustered form of gephyrin contributes to post-Golgi transport and cell surface delivery of GlyRs (reviewed in Ref 27 ).…”

Section: Postsynaptic Gephyrin Clusteringmentioning

confidence: 99%

Gephyrin: a master regulator of neuronal function?

2014

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The neurotransmitters GABA and glycine mediate fast synaptic inhibition by activating ligandgated chloride channels-namely, type A GABA (GABA(A)) and glycine receptors. Both types of receptors are anchored postsynaptically by gephyrin, which self-assembles into a scaffold and interacts with the cytoskeleton. Current research indicates that postsynaptic gephyrin clusters are dynamic assemblies that are held together and regulated by multiple protein-protein interactions. Moreover, post-translational modifications of gephyrin regulate the formation and plasticity of GABAergic synapses by altering the clustering properties of postsynaptic scaffolds and thereby the availability and function of receptors and other signalling molecules. Here, we discuss the formation and regulation of the gephyrin scaffold, its role in GABAergic and glycinergic synaptic function and the implications for the pathophysiology of brain disorders caused by abnormal inhibitory neurotransmission. Shiva Tyagarajan graduated as a molecular virologist at the Pennsylvania State University (USA) and later trained as a neurobiologist during his post-doctoral studies at the University of Zurich. He is currently a group leader and the research focus of his group is to elucidate molecular and cellular mechanisms that couple transcriptional and post-transcriptional programs to regulate GABAergic synaptic plasticity. 3 AbstractThe neurotransmitters GABA and glycine mediate fast synaptic inhibition by activating ligand-gated Cl  channels, namely the GABA A and glycine receptors. Both types of receptors are anchored postsynaptically by gephyrin, which self-assembles into a scaffold and interacts with the cytoskeleton. Current research indicates that gephyrin postsynaptic clusters are dynamic assemblies that are held together and regulated by multiple protein-protein interactions. Moreover, posttranslational modifications of gephyrin regulate the formation and plasticity of GABAergic synapses, by altering the clustering properties of postsynaptic scaffolds and thereby the availability and function of receptors and other signalling molecules.Here, we discuss the formation and regulation of the gephyrin scaffold, its role in GABAergic and glycinergic synaptic function and the implications for the pathophysiology of brain disorders caused by abnormal inhibitory neurotransmission.On-line summary  Gephyrin is a multi-functional protein, responsible for Moco biosynthesis in all organisms, and for postsynaptic clustering of glycine receptors and GABAA receptors in vertebrate CNS  Gephyrin forms a protein scaffold by self-assembly from trimeric complexes, which interacts with numerous, structurally different proteins, in order to form a high ordered signalling complex in glycinergic and GABAergic synapses  Gephyrin function as a scaffolding protein is regulated by alternate mRNA splicing and by multiple post-transcriptional and posttranslational modifications, which only begin to be understood.  Regulation of gephyrin scaffold by multiple signallin...

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“…Thrombospondins are elevated during synaptogenesis associated with development and are also elevated after nerve injury. However, thrombospondins promote formation of nonfunctional silent synapses (Christopherson et al, 2005), and thrombospondins destabilize postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (Hennekinne et al, 2013). The involvement of gabapentin in these processes remains unclear.…”

mentioning

confidence: 99%