Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses.
Activity-dependent plasticity in the brain arises in part from changes in the number of synaptic AMPA receptors. Synaptic trafficking of AMPA receptors is controlled by stargazin and homologous transmembrane AMPA receptor regulatory proteins (TARPs). We found that TARPs were stable at the plasma membrane, whereas AMPA receptors were internalized in a glutamate-regulated manner. Interaction with AMPA receptors involved both extra- and intracellular determinants of TARPs. Upon binding to glutamate, AMPA receptors detached from TARPs. This did not require ion flux or intracellular second messengers. This allosteric mechanism for AMPA receptor dissociation from TARPs may participate in glutamate-mediated internalization of receptors in synaptic plasticity.
Department of Physiology, University of California, San Francisco, San Francisco, CA 94143-2140, USA.
Susumu
S
Tomita
Masaki
M
Fukata
Roger A
RA
Nicoll
David S
DS
Bredt
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology; D004705:Endocytosis; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009473:Neuronal Plasticity; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015220:Calcium Channels; D018698:Glutamic Acid; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C491912:CACNG2 protein, human; C491911:Cacng2 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2