Receptor activation and homer differentially control the lateral mobility of metabotropic glutamate receptor 5 in the neuronal membrane.
Glutamate receptors are clustered at the membrane through interactions with intracellular scaffolding proteins and cytoskeletal elements but can also be found in intracellular compartments or dispersed in the membrane. This distribution results from an equilibrium between the different pools of receptors whose dynamic is poorly known. The group I metabotropic glutamate receptor 5 (mGluR5) is concentrated in an annulus around the postsynaptic density but also found in large amounts in the extrasynaptic membrane. To analyze the dynamic of stabilization of mGluR5, we used single-particle tracking, force measurements, and fluorescence recovery to measure the mobility of mGluR5. We found that receptor activation increases receptor diffusion, whereas the scaffolding protein Homer favors confinement of receptor movements within clusters of Homer-mGluR5. However, this stabilization is reversible, because even in the presence of Homer, receptors still enter and exit from clusters at fast rates. Furthermore, clusters themselves are highly dynamic both in their movements and in their composition, which can vary within tens of seconds. Thus, exchange of receptors between dispersed and clustered states is fast and regulated during physiological processes. These properties may explain certain fast changes in receptor composition observed at postsynaptic densities.
Sergé
Arnauld
A
Physiologie Cellulaire de la Synapse, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5091, Institut François Magendie, 33077 Bordeaux, France.
Fourgeaud
Lawrence
L
Hémar
Agnès
A
Choquet
Daniel
D
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004058:Diffusion / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics; D018715:Microscopy, Video; D008863:Microspheres; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D011940:Receptor Aggregation / Q000187:drug effects / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; C578937:Grm5 protein, rat; D000072233:Homer Scaffolding Proteins; D008164:Luminescent Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins