Cellular transport and membrane dynamics of the glycine receptor

Dumoulin, Andréa

doi:10.3389/neuro.02.028.2009

Cited by 34 publications

(38 citation statements)

References 114 publications

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“…However, the binding of glycine molecules to the receptor displays a strong cooperativity (Legendre, 2001;Burzomato et al, 2004), whereby IPSC kinetics are likely related to the magnitude of the glycine transient in the cleft and to allosteric modulation of the receptor (Fucile et al, 2000;Suwa et al, 2001). In addition, the kinetics of glycinergic currents depend on the receptor membrane density (Taleb and Betz, 1994;De Saint Jan et al, 2001;Legendre et al, 2002), so that glycinergic kinetics could be rapidly modified via the activity-dependent modulation of the density of postsynaptic GlyR (Lévi et al, 2008;Dumoulin et al, 2009). Immunohistochemical data and paired recordings suggest that such a regulation of GlyR density, rather than the variability in presynaptic transmitter content, might occur in UBCs and cause kinetics variability.…”

Section: Different Dynamic Properties Of the Gaba And Glycine Componentsmentioning

confidence: 99%

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Rousseau¹,

Dugué²,

Dumoulin³

et al. 2012

J. Neurosci.

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Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory-inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABA A receptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.

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Section: Different Dynamic Properties Of the Gaba And Glycine Componentsmentioning

confidence: 99%

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Rousseau¹,

Dugué²,

Dumoulin³

et al. 2012

J. Neurosci.

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“…The tail region of KIFs interacts with adaptor proteins, which recognize cargos containing specific molecules to be transported (Hirokawa et al, 2010;Hirokawa et al, 2009;Kardon and Vale, 2009;Millecamps and Julien, 2013). An appropriate combination of a motor protein and an adaptor protein appears to be important for accurate targeting of synaptic components (Dumoulin et al, 2009;Jeyifous et al, 2009;Setou et al, 2002;Terauchi and Umemori, 2012;Washbourne et al, 2004;Zheng et al, 2011). Here, we examine how the two presynaptic organizers FGF22 and FGF7 are transported to the appropriate locations so that they act as synapsetype-specific organizing molecules.…”

Section: Introductionmentioning

confidence: 99%

Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers, FGF22 and FGF7

Terauchi

Timmons

Kikuma

et al. 2014

Journal of Cell Science

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Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations -FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer.

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“…Scaffolding proteins ensure accurate localization of neurotransmitter receptors at synaptic sites, thereby controlling both long-term stability as well as plasticity of synapses (1). At inhibitory synapses the scaffolding protein gephyrin provides docking sites for glycine receptors (GlyRs) 2 and GABA A receptors (GABA A R) (2).…”

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confidence: 99%

Splice-specific Glycine Receptor Binding, Folding, and Phosphorylation of the Scaffolding Protein Gephyrin

Herweg

Schwarz

2012

Journal of Biological Chemistry

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Background: Gephyrin is a postsynaptic scaffolding protein at inhibitory synapses and undergoes alternative splicing. Results: Gephyrin splice variants expressed in insect cells were purified as stable hexamers and high-oligomers. Splice-specific folding and stability, glycine receptor ␤-loop binding, and phosphorylation of gephyrin were found. Conclusion: Splicing and phosphorylation controls gephyrin clustering via conformational changes within the C domain. Significance: Novel regulatory circuits controlling gephyrin clustering.

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Cellular transport and membrane dynamics of the glycine receptor

Cited by 34 publications

References 114 publications

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers, FGF22 and FGF7

Splice-specific Glycine Receptor Binding, Folding, and Phosphorylation of the Scaffolding Protein Gephyrin

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