Stargazin modulates AMPA receptor gating and trafficking by distinct domains.
AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors mediate fast excitatory synaptic transmission in the brain. These ion channels rapidly deactivate and desensitize, which determine the time course of synaptic transmission. Here, we find that the AMPA receptor interacting protein, stargazin, not only mediates AMPA receptor trafficking but also shapes synaptic responses by slowing channel deactivation and desensitization. The cytoplasmic tail of stargazin determines receptor trafficking, whereas the ectodomain controls channel properties. Stargazin alters AMPA receptor kinetics by increasing the rate of channel opening. Disrupting the interaction of stargazin ectodomain with hippocampal AMPA receptors alters the amplitude and shape of synaptic responses, establishing a crucial function for stargazin in controlling the efficacy of synaptic transmission in the brain.
Tomita
Susumu
S
Department of Physiology.
Adesnik
Hillel
H
Sekiguchi
Masayuki
M
Zhang
Wei
W
Wada
Keiji
K
Howe
James R
JR
Nicoll
Roger A
RA
Bredt
David S
DS
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004553:Electric Conductivity; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D014982:Xenopus laevis
D015220:Calcium Channels; D018698:Glutamic Acid; D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4