TARP gamma-8 controls hippocampal AMPA receptor number, distribution and synaptic plasticity.
Synaptic plasticity involves activity-dependent trafficking of AMPA-type glutamate receptors. Numerous cytoplasmic scaffolding proteins are postulated to control AMPA receptor trafficking, but the detailed mechanisms remain unclear. Here, we show that the transmembrane AMPA receptor regulatory protein (TARP) gamma-8, which is preferentially expressed in the mouse hippocampus, is important for AMPA receptor protein levels and extrasynaptic surface expression. By controlling the number of AMPA receptors, gamma-8 is also important in long-term potentiation, but not long-term depression. This study establishes gamma-8 as a critical protein for basal AMPA receptor expression and localization at extrasynaptic sites in the hippocampus and raises the possibility that TARP-dependent control of AMPA receptors during synapse development and plasticity may be widespread.
Rouach
Nathalie
N
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA.
Byrd
Keith
K
Petralia
Ronald S
RS
Elias
Guillermo M
GM
Adesnik
Hillel
H
Tomita
Susumu
S
Karimzadegan
Siavash
S
Kealey
Colin
C
Bredt
David S
DS
Nicoll
Roger A
RA
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015139:Blotting, Southern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000172:deficiency / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection / Q000379:methods; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D009687:Nuclear Proteins; D018091:Receptors, AMPA; C413185:TARP; D049452:Green Fluorescent Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid