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Science 28 September 1990:
Vol. 249. no. 4976, pp. 1580 - 1585
DOI: 10.1126/science.1699275
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Articles

Science, Vol 249, Issue 4976, 1580-1585
Copyright © 1990 by American Association for the Advancement of Science

articles

Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS

B Sommer, K Keinanen, TA Verdoorn, W Wisden, N Burnashev, A Herb, M Kohler, T Takagi, B Sakmann, and PH Seeburg

Laboratory of Molecular Neuroendocrinology, Center for Molecular Biology, University of Heidelberg, F.R.G.

In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.


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Selective Regulation of Agrin mRNA Induction and Alternative Splicing in PC12 Cells by Ras-dependent Actions of Nerve Growth Factor.
M. A. Smith, G. R. Fanger, L. T. O'Connor, P. Bridle, and R. A. Maue (1997)
J. Biol. Chem. 272, 15675-15681
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Activation and Desensitization of Hippocampal Kainate Receptors.
T. J. Wilding and J. E. Huettner (1997)
J. Neurosci. 17, 2713-2721
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An Alanine Residue in the M3-M4 Linker Lines the Glycine Binding Pocket of the N-Methyl-D-aspartate Receptor.
M. W. Wood, H. M.A. VanDongen, and A. M.J. VanDongen (1997)
J. Biol. Chem. 272, 3532-3537
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Cellular, Subcellular, and Subsynaptic Distribution of AMPA-Type Glutamate Receptor Subunits in the Neostriatum of the Rat.
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J. Neurosci. 17, 819-833
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G. T. Swanson, S. K. Kamboj, and S. G. Cull-Candy (1997)
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J. Neurosci. 16, 6634-6647
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A Venus Flytrap Mechanism for Activation and Desensitization of alpha -Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptors.
I. Mano, Y. Lamed, and V. I. Teichberg (1996)
J. Biol. Chem. 271, 15299-15302
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Characterization of the Ligand-binding Domains of Glutamate Receptor (GluR)-B and GluR-D Subunits Expressed in Escherichia coli as Periplasmic Proteins.
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Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines.
S. Traynelis, M Hartley, and S. Heinemann (1995)
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Editing of [IMAGE]-Amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Receptor GluR-B Pre-mRNA in Vitro Reveals Site-selective Adenosine to Inosine Conversion.
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J Psychopharmacol 8, 196-203
   Abstract »    PDF »
Molecular diversity of glutamate receptors and implications for brain function.
S Nakanishi (1992)
Science 258, 597-603
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Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor.
N Burnashev, R Schoepfer, H Monyer, J. Ruppersberg, W Gunther, P. Seeburg, and B Sakmann (1992)
Science 257, 1415-1419
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Calcium-permeable AMPA-kainate receptors in fusiform cerebellar glial cells.
N Burnashev, A Khodorova, P Jonas, P. Helm, W Wisden, H Monyer, P. Seeburg, and B Sakmann (1992)
Science 256, 1566-1570
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Elementary steps in synaptic transmission revealed by currents through single ion channels.
B Sakmann (1992)
Science 256, 503-512
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Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases.
L. Wang, M. Salter, and J. MacDonald (1991)
Science 253, 1132-1135
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Structural determinants of ion flow through recombinant glutamate receptor channels.
T. Verdoorn, N Burnashev, H Monyer, P. Seeburg, and B Sakmann (1991)
Science 252, 1715-1718
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Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain.
K. Houamed, J. Kuijper, T. Gilbert, B. Haldeman, P. O'Hara, E. Mulvihill, W Almers, and F. Hagen (1991)
Science 252, 1318-1321
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Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition.
M Hollmann, M Hartley, and S Heinemann (1991)
Science 252, 851-853
   Abstract »    PDF »
Permeation of calcium ions through non-NMDA glutamate channels in retinal bipolar cells.
T. Gilbertson, R Scobey, and M Wilson (1991)
Science 251, 1613-1615
   Abstract »    PDF »
A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing.
A. D. Polydorides, H. J. Okano, Y. Y. L. Yang, G. Stefani, and R. B. Darnell (2000)
PNAS 97, 6350-6355
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