ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Heat shock cognate protein 70 regulates gephyrin clustering.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
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- Preliminary Proteomic Study of the Porcine Pituitary Gland under Heat Stress.Life (Basel, Switzerland) · 2024Article
- Social isolation induces neuroinflammation and microglia overactivation, while dihydromyricetin prevents and improves them.Journal of neuroinflammation · 2022Article
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- Social Isolation Induces Neuroinflammation And Microglia Overactivation, While Dihydromyricetin Prevents And Improves Them.Research square · 2021Article
- Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves Anxiety.Frontiers in pharmacology · 2020Article
- Article
- Gephyrin: a key regulatory protein of inhibitory synapses and beyond.Histochemistry and cell biology · 2018Review
- Estradiol modulates the efficacy of synaptic inhibition by decreasing the dwell time of GABAProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Subcellular distribution of non-muscle myosin IIb is controlled by FILIP through Hsc70.PloS one · 2017Article
- The Molecular Chaperone Hsc70 Interacts with Tyrosine Hydroxylase to Regulate Enzyme Activity and Synaptic Vesicle Localization.The Journal of biological chemistry · 2016Article
- Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival.Progress in retinal and eye research · 2016Review
- Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.Molecular and cellular biology · 2015Article
- Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory.Nature communications · 2015Article
- Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.PLoS genetics · 2014Article
- Differential GABAergic and glycinergic inputs of inhibitory interneurons and Purkinje cells to principal cells of the cerebellar nuclei.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Gephyrin: a master regulator of neuronal function?Nature reviews. Neuroscience · 2014Review
- Heat shock proteins in the brain: role of Hsp70, Hsp 27, and HO-1 (Hsp32) and their therapeutic potential.Translational stroke research · 2013Review
- Glycine receptor mouse mutants: model systems for human hyperekplexia.British journal of pharmacology · 2013Review
- Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice.The Journal of biological chemistry · 2013Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Formation and stabilization of postsynaptic glycine receptor (GlyR) clusters result from their association with the polymerized scaffold protein gephyrin. At the cell surface, lateral diffusion and local trapping of GlyR by synaptic gephyrin clusters is one of the main factors controlling their number. However, the mechanisms regulating gephyrin/GlyR cluster sizes are not fully understood. To identify molecular binding partners able to control gephyrin cluster stability, we performed pull-down assays with full-length or truncated gephyrin forms incubated in a rat spinal cord extract, combined with mass spectrometric analysis. We found that heat shock cognate protein 70 (Hsc70), a constitutive member of the heat shock protein 70 (Hsp70) family, selectively binds to the gephyrin G-domain. Immunoelectron microscopy of mouse spinal cord sections showed that Hsc70 could be colocalized with gephyrin at inhibitory synapses. Furthermore, ternary Hsc70-gephyrin-GlyR coclusters were formed following transfection of COS-7 cells. Upon overexpression of Hsc70 in mouse spinal cord neurons, synaptic accumulation of gephyrin was significantly decreased, but GlyR amounts were unaffected. In the same way, Hsc70 inhibition increased gephyrin accumulation at inhibitory synapses without modifying GlyR clustering. Single particle tracking experiments revealed that the increase of gephyrin molecules reduced GlyR diffusion rates without altering GlyR residency at synapses. Our findings demonstrate that Hsc70 regulates gephyrin polymerization independently of its interaction with GlyR. Therefore, gephyrin polymerization and synaptic clustering of GlyR are uncoupled events.
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