Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability.
Scaffolding proteins interact with membrane receptors to control signaling pathways and cellular functions. However, the dynamics and specific roles of interactions between different components of scaffold complexes are poorly understood because of the dearth of methods available to monitor binding interactions. Using a unique combination of single-cell bioluminescence resonance energy transfer imaging in living neurons and electrophysiological recordings, in this paper, we depict the role of glutamate receptor scaffold complex remodeling in space and time to control synaptic transmission. Despite a broad colocalization of the proteins in neurons, we show that spine-confined assembly/disassembly of this scaffold complex, physiologically triggered by sustained activation of synaptic NMDA (N-methyl-d-aspartate) receptors, induces physical association between ionotropic (NMDA) and metabotropic (mGlu5a) synaptic glutamate receptors. This physical interaction results in an mGlu5a receptor-mediated inhibition of NMDA currents, providing an activity-dependent negative feedback loop on NMDA receptor activity. Such protein scaffold remodeling represents a form of homeostatic control of synaptic excitability.
Centre national de la recherche scientifique, UMR-5203, Institut de Génomique Fonctionnelle, F-34000 Montpellier, Cedex 16, France.
Enora
E
Moutin
Fabrice
F
Raynaud
Jonathan
J
Roger
Emilie
E
Pellegrino
Vincent
V
Homburger
Federica
F
Bertaso
Vincent
V
Ollendorff
Joël
J
Bockaert
Laurent
L
Fagni
Julie
J
Perroy
D000818:Animals; D049229:Dendritic Spines / Q000502:physiology*; D057809:HEK293 Cells; D006624:Hippocampus / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D051381:Rats; D017470:Receptors, Glutamate / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D017470:Receptors, Glutamate