Multiple Association States between Glycine Receptors and Gephyrin Identified by SPT Analysis

Ehrensperger, Marie-Virginie; Hanus, Cyril; Vannier, Christian; Triller, Antoine; Dahan, Maxime

doi:10.1529/biophysj.106.095596

Cited by 116 publications

(171 citation statements)

References 51 publications

(90 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%

“…These results not only support the notion that extrasynaptic GlyRs can diffuse in a gephyrin-bound state (Ehrensperger et al, 2007) but also demonstrate that the diffusion of extrasynaptic GlyR-gephyrin complexes can be modified by factors able to interfere with gephyrin oligomerization.…”

Section: Changes In Glyr Diffusion In Spinal Cord Neuronssupporting

confidence: 79%

“…As described previously (Bonneau et al, 2005;Bannai et al, 2006;Ehrensperger et al, 2007), tracking of single QDs, which were identified by their fluorescence intermittence, was performed with MATLAB (MathWorks) using a homemade macro that accounts for blinking in the fluorescence signal. In brief, the method consists of two main steps, applied successively to each frame of the sequence.…”

Section: Methodsmentioning

confidence: 99%

“…Analyses of mean square displacement (MSD) and initial diffusion coefficient (D) are reported in Bannai et al (2006) and Ehrensperger et al (2007). Briefly, physical parameters can be extracted from each trajectory (x(),y()) by computing the MSD (Saxton and Jacobson, 1997), determined from the following formula:…”

Section: Methodsmentioning

confidence: 99%

“…Among these proteins, gephyrin is the core molecule for anchoring and stabilizing glycine and GABA A receptors (GlyR and GABA A R) at inhibitory postsynaptic sites (Kirsch et al, 1993;Meier et al, 2001;Fritschy et al, 2008;Tretter et al, 2008). The dynamic regulation of GlyR clustering is not based exclusively on the association between the receptor and gephyrin, since at least 40% of GlyRs diffusing outside of synapses are bound to gephyrin (Ehrensperger et al, 2007). Therefore, in addition to gephyrin-GlyR interactions, gephyrin-gephyrin interactions also have to be taken into account.…”

Section: Introductionmentioning

confidence: 99%

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Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering

Calamai

Specht²,

Heller³

et al. 2009

Journal of Neuroscience

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: 79%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering

Calamai

Specht²,

Heller³

et al. 2009

Journal of Neuroscience

149

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Chemical Synapses

Thiele

Nash

2010

Encyclopedia of Life Sciences

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Chemical synapses are among the most elaborate junctions existing between two cells, enabling communication between neurons through chemical neurotransmission within milliseconds. This fast rate of transmission is achieved through three subsynaptic compartments; the presynaptic bouton, the synaptic cleft and the postsynaptic junction. The presynaptic bouton packages neurotransmitters into synaptic vesicles then releases them into the synaptic cleft. Release of synaptic vesicles occurs through several distinct stages, coordinated by a group of specialised proteins. The postsynaptic density (PSD) has evolved into a complex neurotransmitter reception apparatus, which enables the postsynaptic terminal to modulate the downstream response to neurotransmitters. Following activation of receptors on the postsynaptic membrane, neurotransmitters are taken back up into the presynaptic bouton and repackaged into synaptic vesicles (SVs). The synaptic cleft contains proteins that ensure that active zone and PSD remain in proximity. These proteins are also required during synaptogenesis to ensure that the synapse forms properly. Key Concepts: There are three major structural components that define the synapse: the presynaptic bouton (also known as presynaptic terminal), postsynaptic junction (also known as postsynaptic terminal) and the synaptic cleft. The presynaptic bouton is responsible for packaging neurotransmitters into synaptic vesicles, then releasing their contents into the synaptic cleft in response to calcium influx. Synaptic vesicles are released at a specialised site within the presynaptic bouton known as the active zone. Synaptic vesicles are released by a process known as exocytosis through several distinct steps involving specialised proteins that form a highly interactive and dynamic protein complex at the site of synaptic vesicle release. Interpretation of the presynaptic message takes place at the postsynaptic membrane through transmembrane proteins called receptors. The postsynaptic density is situated adjacent to the postsynaptic membrane within the postsynaptic terminal, juxtaposed to the presynaptic active zone. The postsynaptic density is composed of receptors, scaffolding and adhesion proteins, kinases and phosphatases, as well as cytoskeletal elements, which are linked together to form macromolecular complexes. The postsynaptic density of excitatory synapses is thicker (more pronounced) than the postsynaptic density of inhibitory synapses. The synaptic cleft is a narrow space, approximately 20–30 nm wide situated between the presynaptic and the postsynaptic plasma membranes. The synaptic cleft is composed of proteinaceous and carbohydrate‐rich cell adhesion molecules.

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