Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane

Charrier, Cécile; Ehrensperger, Marie-Virginie; Dahan, Maxime; Lévi, Sabine; Triller, Antoine

doi:10.1523/jneurosci.1758-06.2006

Cited by 125 publications

(146 citation statements)

References 64 publications

(87 reference statements)

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“…4 A). In agreement with previous results (Dahan et al, 2003;Charrier et al, 2006;Ehrensperger et al, 2007), synaptic GlyRs displayed a confined mobility (Fig. 4 B), whereas extrasynaptic receptor had the features characteristic of free Brownian diffusion (Fig.…”

Section: Changes In Glyr Diffusion In Spinal Cord Neuronssupporting

confidence: 93%

“…The median D values obtained for synaptic and extrasynaptic GlyRs were consistent with previous data (Charrier et al, 2006). The analysis of synaptic trajectories of GlyRs yielded comparable values of D in the presence of the various constructs (Table 1, Fig.…”

Section: Changes In Glyr Diffusion In Spinal Cord Neuronssupporting

confidence: 89%

“…As a consequence, the mobility of the complex would be increased, particularly when taking into account the crowded cytoplasmic environment. Additionally, specific interactions such as those between the GlyR-gephyrin complex and the cytoskeleton may contribute to slowing down the receptor (Charrier et al, 2006;Hanus et al, 2006;Maas et al, 2006). The higher diffusion coefficients of extrasynaptic receptor complexes are thus likely to result not only from their lower molecular size but also from the reduced number of binding sites available for specific interactions with other proteins.…”

Section: Gephyrin Clustering and Glyr Diffusionmentioning

confidence: 99%

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Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering

Calamai

Specht²,

Heller³

et al. 2009

Journal of Neuroscience

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149

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High local concentrations of glycine receptors (GlyRs) at inhibitory postsynaptic sites are achieved through their binding to the scaffold protein gephyrin. The N-and C-terminal domains of gephyrin are believed to trimerize and dimerize, respectively, thus contributing to the formation of submembranous gephyrin clusters at synapses. GlyRs are associated with gephyrin also at extrasynaptic locations. We have investigated how gephyrin oligomerization influences GlyR dynamics and clustering in COS-7 cells and in cultured spinal cord neurons. To this aim, we have expressed isolated N-and C-terminal domains of gephyrin that interfere with the oligomerization of the full-length protein. We also studied the effect of an endogenous splice variant, ge(2,4,5), with a decreased propensity to trimerize. A reduction of the size and number of gephyrin-GlyR clusters was found in cells expressing the various interfering gephyrin constructs. Using fluorescence recovery after photobleaching, we studied the exchange kinetics of synaptic gephyrin clusters. Real-time singleparticle tracking was used to analyze the mobility of GlyRs. We found that all the tested constructs displayed faster rates of recovery than wild-type gephyrin and increased the mobility of extrasynaptic receptors, showing that gephyrin-gephyrin interactions modulate the lateral diffusion of GlyRs. Furthermore, we observed an inverse correlation between GlyR diffusion properties and gephyrin cluster size that depended on the number of binding sites blocked by the different constructs. Since alterations in the oligomerization properties of gephyrin are related to the dynamics of GlyRs, the gephyrin splice variant ge(2,4,5) may be implicated in the modulation of synaptic strength.

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Section: Changes In Glyr Diffusion In Spinal Cord Neuronssupporting

confidence: 93%

Section: Changes In Glyr Diffusion In Spinal Cord Neuronssupporting

confidence: 89%

Section: Gephyrin Clustering and Glyr Diffusionmentioning

confidence: 99%

See 1 more Smart Citation

Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering

Calamai

Specht²,

Heller³

et al. 2009

Journal of Neuroscience

Self Cite

149

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“…Such is the case for the excitatory glutamate AMPA receptors (Allison et al, 1998) and for glycine receptors (GlyRs) (Kirsch and Betz, 1995). This control results in part from the regulation of the physical characteristics (confinement and trapping) of lateral receptor diffusion, as demonstrated for GlyRs in spinal cord neurons (Charrier et al, 2006). However, several receptors and transmembrane proteins of the postsynaptic density (PSD) purify with detergent-resistant membrane (DRM) fractions, indicating a possible association with lipid rafts.…”

Section: Introductionmentioning

confidence: 99%

Control of the Postsynaptic Membrane Viscosity

Renner

Choquet²,

Triller³

2009

J. Neurosci.

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139

154

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The physical properties of the postsynaptic membrane (PSM), including its viscosity, determine its capacity to regulate the net flux of synaptic membrane proteins such as neurotransmitter receptors. To address these properties, we studied the lateral diffusion of glycophosphatidylinositol-anchored green fluorescent protein and cholera toxin bound to the external leaflet of the plasma membrane. Relative to extrasynaptic regions, their mobility was reduced at synapses and even more at inhibitory than at excitatory ones. This indicates a higher density of obstacles and/or higher membrane viscosity at inhibitory contacts. Actin depolymerization reduced the confinement and accelerated a population of fast, mobile molecules. The compaction of obstacles thus depends on actin cytoskeleton integrity. Cholesterol depletion increased the mobility of the slow diffusing molecules, allowing them to diffuse more rapidly through the crowded PSM. Thus, the PSM has lipid-raft properties, and the density of obstacles to diffusion depends on filamentous actin. Therefore, lipid composition and actin-dependent protein compaction regulate viscosity of the PSM and, consequently, the molecular flow in and out of synapses.

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“…Closer insights into the nature of the interactions of gephyrin with the cytoskeleton were derived from a recent study using single particle tracking of GlyRs to assess the eVects of a pharmacological dissolution of Wlamentous cytoskeletal elements (Charrier et al 2006). In this study both F-actin and microtubule disruption were demonstrated to increase GlyR exchanges between synaptic and extrasynaptic membranes and simultaneously decreasing receptor dwell time at synapses.…”

Section: Analysis Of Gephyrin Dewcient Micementioning

confidence: 86%

Molecular architecture of glycinergic synapses

Dresbach

Nawrotzki

Kremer

et al. 2008

Histochem Cell Biol

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Synapses can be considered chemical machines, which are optimized for fast and repeated exocytosis of neurotransmitters from presynaptic nerve terminals and the reliable electrical or chemical transduction of neurotransmitter binding to the appropriate receptors in the postsynaptic membrane. Therefore, synapses share a common repertoire of proteins like, e.g., the release machinery and certain cell adhesion molecules. This basic repertoire must be extended in order to generate speciWcity of neurotransmission and allow plastic changes, which are considered the basis of developmental and/or learning processes. Here, we focus on these complementary molecules located in the presynaptic terminal and postsynaptic membrane specializations of glycinergic synapses. Moreover, as speciWcity of neurotransmission in this system is established by the speciWc binding of the neurotransmitter to its receptor, we review the molecular properties of glycine receptor subunits and their assembly into functional glycine receptors with diVerent functional characteristics. The past years have revealed that the molecular machinery underlying inhibitory and especially glycinergic postsynaptic membrane specializations is more complex and dynamic than previously anticipated from morphological studies. The emerging features include structural components as well as signaling modules, which could confer the plasticity required for the proper function of distinct motor and sensory functions.

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Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane

Cited by 125 publications

References 64 publications

Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering

Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering

Control of the Postsynaptic Membrane Viscosity

Molecular architecture of glycinergic synapses

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