A mechanism underlying AMPA receptor trafficking during cerebellar long-term potentiation.
Long-term potentiation (LTP) is mediated by the activity-driven delivery of GluR1 glutamate receptors via Ca2+/calmodulin-dependent protein kinase II activity in various brain regions. Recently, postsynaptic LTP was shown to be induced at parallel fiber-Purkinje cell synapses by stimulating the parallel fibers at 1 Hz or applying a NO donor. Here, we demonstrate that NO-evoked postsynaptic LTP in mice cerebellum was blocked by botulinum toxin and enhanced by prior treatment with phorbol ester, which is known to induce GluR2 endocytosis. Interestingly, such LTP was not affected by a Ca2+/calmodulin-dependent protein kinase II inhibitor or a peptide binding to a protein interacting with C kinase 1, but was blocked by a peptide binding to N-ethylmaleimide-sensitive factor, which specifically binds to GluR2. Therefore, although the synaptic incorporation of GluR2 has been reported to be a constitutive pathway, NO-induced postsynaptic LTP in Purkinje cells is likely mediated by a pathway involving N-ethylmaleimide-sensitive factor-dependent GluR2 trafficking.
Kakegawa
Wataru
W
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Yuzaki
Michisuke
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D004594:Electrophysiology; D004789:Enzyme Activation; D005089:Exocytosis; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011689:Purkinje Cells / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D018091:Receptors, AMPA; D009569:Nitric Oxide; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D052066:N-Ethylmaleimide-Sensitive Proteins; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium