A mechanism underlying AMPA receptor trafficking during cerebellar long-term potentiation
- Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
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Communicated by Roger Y. Tsien, University of California at San Diego, La Jolla, CA, October 11, 2005 (received for review June 30, 2005)
Abstract
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.
Footnotes
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↵ * To whom correspondence should be addressed. E-mail: myuzaki{at}sc.itc.keio.ac.jp.
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Author contributions: W.K. and M.Y. designed research; W.K. performed research; W.K. analyzed data; and W.K. and M.Y. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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Abbreviations: AC, adenylate cyclase; AIP, autocamtide-2 related inhibitory peptide; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor; BAPTA, 1,2-bis-(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; BoTx, botulinum toxin; CaMKII, Ca2+/calmodulin-dependent protein kinase II; CARP, Ca2+-permeable AMPAR plasticity; DEANO, diethylamine NO sodium salt; EPSC, excitatory postsynaptic current; LTD, long-term depression; LTP, long-term potentiation; NMDAR, N-methyl-d-aspartate-type glutamate receptor; NSF, N-ethylmaleimide-sensitive factor; PF, parallel fiber; PICK1, protein interacting with C kinase 1; PPF, paired-pulse facilitation; SNARE, soluble NSF attachment protein receptor; TPA, 12-O-tetradecanoyl-phorbol-13-acetate.
- Copyright © 2005, The National Academy of Sciences
