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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzylamines / pharmacology
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Biotinylation / methods
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Embryo, Mammalian
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Fibrinogen / pharmacology
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Integrin beta1 / metabolism*
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Integrin beta1 / pharmacology
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Integrin beta3 / metabolism*
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Integrin beta3 / pharmacology
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Mass Spectrometry / methods
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Neurons / drug effects
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Neurons / physiology*
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Patch-Clamp Techniques / methods
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Phosphorylation
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Photobleaching
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Protein Kinase Inhibitors / pharmacology
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Protein Transport / drug effects
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Protein Transport / physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, Glycine / genetics
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Receptors, Glycine / metabolism*
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Spinal Cord / cytology
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Statistics, Nonparametric
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Sulfonamides / pharmacology
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Synapses / drug effects
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Synapses / physiology*
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Thrombospondin 1 / pharmacology
Substances
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Benzylamines
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Carrier Proteins
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Integrin beta1
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Integrin beta3
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Membrane Proteins
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Protein Kinase Inhibitors
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Receptors, Glycine
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Sulfonamides
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Thrombospondin 1
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gephyrin
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KN 93
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Fibrinogen