Abstract
The regulation of glycine receptor (GlyR) number at synapses is necessary for the efficacy of inhibition and the control of neuronal excitability in the spinal cord. GlyR accumulation at synapses depends on the scaffolding molecule gephyrin and is linked to GlyR synaptic dwell time. However, the mechanisms that tune GlyR synaptic exchanges in response to different neuronal environments are unknown. Integrins are cell adhesion molecules and signaling receptors. Using single quantum dot imaging and fluorescence recovery after photobleaching, we found in rats that β1 and β3 integrins adjust synaptic strength by regulating the synaptic dwell time of both GlyRs and gephyrin. β1 and β3 integrins crosstalked via calcium/calmodulin-dependent protein kinase II and adapted GlyR lateral diffusion and gephyrin-dependent trapping at synapses. This provides a mechanism for maintaining or adjusting the steady state of postsynaptic molecule exchanges and the level of glycinergic inhibition in response to neuron- and glia-derived signals or extracellular matrix remodeling.
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Acknowledgements
We thank members of the Triller laboratory, S. Supplisson, K. Aubrey, L. Wang and O. Pascual for kindly providing access to their patch-clamp rig and for helpful discussions, Y. Goda and L. Cingolani for integrin constructs and C. Specht, B. Barbour and R. Miles for critical reading of the manuscript. This work was supported by INSERM (A.T.), Agence Nationale de la Recherche (ANR08BLAN0282; A.T.), Fondation Pierre-Gilles de Gennes (A.T.), Institut pour la Recherche sur la Moelle épinière et l'Encéphale (A.T.), Ministère de la Recherche et de la Technologie (C.C. and P.M.) and Association Française contre les Myopathies (C.C.).
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C.C. designed, performed and analyzed the experiments except for the in vitro phosphorylation assays and mass spectrometry and wrote the manuscript with help from the other authors. P.M. performed the in vitro phosphorylation assays. R.Y.T.-C. and D.R. performed mass spectrometry and analyzed data. I.M.M. supervised mass spectrometry and phosphorylation analyses. A.T. supervised the project.
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Charrier, C., Machado, P., Tweedie-Cullen, R. et al. A crosstalk between β1 and β3 integrins controls glycine receptor and gephyrin trafficking at synapses. Nat Neurosci 13, 1388–1395 (2010). https://doi.org/10.1038/nn.2645
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DOI: https://doi.org/10.1038/nn.2645
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