DRPEER: A Motif in the Extracellular Vestibule Conferring High Ca2+Flux Rates in NMDA Receptor Channels
作者： Junryo Watanabe , Christine Beck , Thomas Kuner , Louis S. Premkumar , Lonnie P. Wollmuth
DOI: 10.1523/JNEUROSCI.22-23-10209.2002
关键词:
摘要: The high flux rate of Ca2+ through NMDA receptor (NMDAR) channels is critical for their biological function and may depend on a binding site in the extracellular vestibule. We screened substitutions hydrophilic residues exposed vestibule identified cluster charged proline, DRPEER motif, positioned C terminal to M3, that unique NR1 subunit. Charge neutralization or conversion altered fractional currents manner consistent with its forming Ca2+. Similarly, mutant channel which all negative charges are neutralized (ARPAAR), block by single-channel current amplitudes attenuated. In these same channels, Mg2+ unaffected. located extracellularly, contribution influx distinct from narrow constriction. conclude key DRPEER, acting as an external Ca2+, along conserved asparagine M3 segment proper, contribute under physiological conditions. Therefore, domains represent molecular determinants NMDAR synaptic physiology.
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P Ascher, L Nowak, The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. The Journal of Physiology. ,vol. 399, pp. 247- 266 ,(1988) , 10.1113/JPHYSIOL.1988.SP017078
Arthur Karlin, Myles H. Akabas, [8] Substituted-cysteine accessibility method Methods in Enzymology. ,vol. 293, pp. 123- 145 ,(1998) , 10.1016/S0076-6879(98)93011-7
MM Zarei, JA Dani, Structural basis for explaining open-channel blockade of the NMDA receptor. The Journal of Neuroscience. ,vol. 15, pp. 1446- 1454 ,(1995) , 10.1523/JNEUROSCI.15-02-01446.1995
Lonnie P. Wollmuth, Thomas Kuner, Bert Sakmann, Intracellular Mg2+interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel The Journal of Physiology. ,vol. 506, pp. 33- 52 ,(1998) , 10.1111/J.1469-7793.1998.00033.X
C. E. Jahr, C. F. Stevens, Calcium permeability of the N-methyl-D-aspartate receptor channel in hippocampal neurons in culture Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 11573- 11577 ,(1993) , 10.1073/PNAS.90.24.11573
Thomas Kuner, Lonnie P. Wollmuth, Arthur Karlin, Peter H. Seeburg, Bert Sakmann, Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines Neuron. ,vol. 17, pp. 343- 352 ,(1996) , 10.1016/S0896-6273(00)80165-8
Ralf Schneggenburger, Philippe Ascher, Coupling of Permeation and Gating in an NMDA-Channel Pore Mutant Neuron. ,vol. 18, pp. 167- 177 ,(1997) , 10.1016/S0896-6273(01)80055-6
H.K.P. Feirabend, H. Choufoer, S. Ploeger, Preservation and Staining of Myelinated Nerve Fibers Methods. ,vol. 15, pp. 123- 131 ,(1998) , 10.1006/METH.1998.0615
Nail Burnashev, Calcium permeability of glutamate-gated channels in the central nervous system. Current Opinion in Neurobiology. ,vol. 6, pp. 311- 317 ,(1996) , 10.1016/S0959-4388(96)80113-9
G. Sharma, C. F. Stevens, Interactions between two divalent ion binding sites in N-methyl-D-aspartate receptor channels. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 14170- 14175 ,(1996) , 10.1073/PNAS.93.24.14170