Ras and Rap control AMPA receptor trafficking during synaptic plasticity.
Recent studies show that AMPA receptor (-R) trafficking is important in synaptic plasticity. However, the signaling controlling this trafficking is poorly understood. Small GTPases have diverse neuronal functions and their perturbation is responsible for several mental disorders. Here, we examine the small GTPases Ras and Rap in the postsynaptic signaling underlying synaptic plasticity. We show that Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery of AMPA-Rs during long-term potentiation. In contrast, Rap mediates NMDA-R-dependent removal of synaptic AMPA-Rs that occurs during long-term depression. Ras and Rap exert their effects on AMPA-Rs that contain different subunit composition. Thus, Ras and Rap, whose activity can be controlled by postsynaptic enzymes, serve as independent regulators for potentiating and depressing central synapses.
Cold Spring Harbor Laboratory, 1 Bungtown Road, NY 11724, USA.
J Julius
JJ
Zhu
Yi
Y
Qin
Mingming
M
Zhao
Linda
L
Van Aelst
Roberto
R
Malinow
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008164:Luminescent Proteins; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009924:Organ Culture Techniques; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013347:Subcellular Fractions; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases; D020668:rap GTP-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D018091:Receptors, AMPA; D015636:Magnesium Chloride; D049452:Green Fluorescent Proteins; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020668:rap GTP-Binding Proteins; D018631:ras Proteins