Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition

被引:161
作者
Zheng, F [1 ]
Gingrich, MB [1 ]
Traynelis, SF [1 ]
Conn, PJ [1 ]
机构
[1] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA
关键词
D O I
10.1038/634
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Activation of the tyrosine kinase Src potentiates NMDA receptor currents, which is thought to be necessary for induction of hippocampal long-term potentiation. Although the carboxy(C)-terminal domain of the NR2A subunit contains potential tyrosine phosphorylation sites, the mechanism by which Src modulates synaptic plasticity and NMDA receptor currents is not fully understood. Here we present evidence from NR1 mutants and splice variants that Src potentiates NMDA-receptor currents by reducing the tonic inhibition of receptors composed of NR1 and NR2A subunits by extracellular zinc. Using site-directed mutagenesis, we have identified three C-terminal tyrosine residues of NR2A that are required for Src's modulation of the zinc sensitivity of NMDA receptors. Our data link two modulatory sites of NMDA receptors that were previously thought to be independent.
引用
收藏
页码:185 / 191
页数:7
相关论文
共 37 条
[1]  
BERS DM, 1994, METHOD CELL BIOL, V40, P3
[2]  
BOGDEN JD, 1977, CLIN CHEM, V23, P485
[3]   BOUND AND DETERMINED - A COMPUTER-PROGRAM FOR MAKING BUFFERS OF DEFINED ION CONCENTRATIONS [J].
BROOKS, SPJ ;
STOREY, KB .
ANALYTICAL BIOCHEMISTRY, 1992, 201 (01) :119-126
[4]   GREEN FLUORESCENT PROTEIN AS A MARKER FOR GENE-EXPRESSION [J].
CHALFIE, M ;
TU, Y ;
EUSKIRCHEN, G ;
WARD, WW ;
PRASHER, DC .
SCIENCE, 1994, 263 (5148) :802-805
[5]   HIGH-EFFICIENCY TRANSFORMATION OF MAMMALIAN-CELLS BY PLASMID DNA [J].
CHEN, C ;
OKAYAMA, H .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (08) :2745-2752
[6]   PROTEIN-KINASE-C REDUCES MG2+ BLOCK OF NMDA-RECEPTOR CHANNELS AS A MECHANISM OF MODULATION [J].
CHEN, L ;
HUANG, LYM .
NATURE, 1992, 356 (6369) :521-523
[7]   Differential sensitivity of recombinant N-methyl-D-aspartate receptor subtypes to zinc inhibition [J].
Chen, NS ;
Moshaver, A ;
Raymond, LA .
MOLECULAR PHARMACOLOGY, 1997, 51 (06) :1015-1023
[8]  
CHRISTINE CW, 1990, J NEUROSCI, V10, P108
[9]   A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation [J].
Dikic, I ;
Tokiwa, G ;
Lev, S ;
Courtneidge, SA ;
Schlessinger, J .
NATURE, 1996, 383 (6600) :547-550
[10]   RAPID DECAY OF AVERAGED SINGLE-CHANNEL NMDA RECEPTOR ACTIVATIONS RECORDED AT LOW AGONIST CONCENTRATION [J].
EDMONDS, B ;
COLQUHOUN, D .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1992, 250 (1329) :279-286