Multiple routes for glutamate receptor trafficking: surface diffusion and membrane traffic cooperate to bring receptors to synapses.
Trafficking of glutamate receptors into and out of synapses is critically involved in the plasticity of excitatory synaptic transmission. Endocytosis and exocytosis of receptors have initially been thought to account alone for this trafficking. However, membrane proteins also traffic through surface lateral diffusion in the plasma membrane. We describe developments in electrophysiological and optical approaches that have allowed for the real-time measurement of glutamate receptor surface trafficking in live neurons. These include (i) specific imaging of surface receptors using a pH-sensitive fluorescent protein; (ii) design of a photoactivable drug to locally inactivate surface receptors and monitor electrophysiologically their recovery; and (iii) application of single-molecule fluorescence microscopy to directly track the movement of individual surface receptors with nanometer resolution inside and outside synapses. Together, these approaches have demonstrated that glutamate receptors diffuse at high rates in the neuronal membrane and suggest a key role for surface diffusion in the regulation of receptor numbers at synapses.
Centre de Physique Moléculaire Optique et Hertzienne, CNRS (UMR 5798) and Université Bordeaux 1, 351 Cours de la Libération, 33405 Talence Cedex, France.
Laurent
L
Cognet
Laurent
L
Groc
Brahim
B
Lounis
Daniel
D
Choquet
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003199:Computer Systems; D004058:Diffusion; D004594:Electrophysiology / Q000379:methods*; D004705:Endocytosis; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005089:Exocytosis; D005456:Fluorescent Dyes / Q000032:analysis; D049452:Green Fluorescent Proteins / Q000032:analysis; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009574:Nitro Compounds / Q000494:pharmacology / Q000528:radiation effects; D010777:Photochemistry; D021381:Protein Transport; D045663:Quantum Dots; D011804:Quinolines / Q000494:pharmacology / Q000528:radiation effects; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D014466:Ultraviolet Rays
C493868:6-azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D009574:Nitro Compounds; D011804:Quinolines; D017470:Receptors, Glutamate; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins