Growth factor-mediated Fyn signaling regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression in rodent neocortical neurons

被引:65
作者
Narisawa-Saito, M
Silva, AJ
Yamaguchi, T
Hayashi, T
Yamamoto, T
Nawa, H [1 ]
机构
[1] Niigata Univ, Inst Brain Res, Dept Mol Neurobiol, Niigata 9518585, Japan
[2] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[3] Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan
关键词
D O I
10.1073/pnas.96.5.2461
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Src-family protein tyrosine kinases (PTKs) transduce signals to regulate neuronal development and synaptic plasticity. However, the nature of their activators and molecular mechanisms underlying these neural processes are unknown. Here, we show that brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor enhance expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepri onic acid (AMPA)-type glutamate receptor 1 and 2/3 proteins in rodent neocortical neurons via the Src-family PTK(s). The increase in AMPA receptor levels was blocked in cultured neocortical neurons by addition of a Src-family-selective PTK inhibitor. Accordingly, neocortical cultures from Fyn-knockout mice failed to respond to BDNF whereas those from wild-type mice responded. Moreover, the neocortex of young Fyn mutants exhibited a significant in vivo reduction in these AMPA receptor proteins but not in their mRNA levels. In vitro kinase assay revealed that BDNF can indeed activate the Fyn kinase: It enhanced tyrosine phosphorylation of Fyn as well as that of enolase supplemented exogenously. All of these results suggest that the Src-family kinase Fyn, activated by the growth factors, plays a crucial role in modulating AMPA receptor expression during brain development.
引用
收藏
页码:2461 / 2466
页数:6
相关论文
共 57 条
[31]   ASSOCIATION BETWEEN THE PDGF RECEPTOR AND MEMBERS OF THE SRC FAMILY OF TYROSINE KINASES [J].
KYPTA, RM ;
GOLDBERG, Y ;
ULUG, ET ;
COURTNEIDGE, SA .
CELL, 1990, 62 (03) :481-492
[32]   Neurotrophins differentially regulate voltage-gated ion channels [J].
Lesser, SS ;
Sherwood, NT ;
Lo, DC .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1997, 10 (3-4) :173-183
[33]   BRAIN-DERIVED NEUROTROPHIC FACTOR RAPIDLY ENHANCES SYNAPTIC TRANSMISSION IN HIPPOCAMPAL-NEURONS VIA POSTSYNAPTIC TYROSINE KINASE RECEPTORS [J].
LEVINE, ES ;
DREYFUS, CF ;
BLACK, IB ;
PLUMMER, MR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :8074-8077
[34]   Physiology of the neurotrophins [J].
Lewin, GR ;
Barde, YA .
ANNUAL REVIEW OF NEUROSCIENCE, 1996, 19 :289-317
[35]  
LOUGHLIN SE, 1993, NEUTROPHIC FACTORS
[36]   Src activation in the induction of long-term potentiation in CA1 hippocampal neurons [J].
Lu, YM ;
Roder, JC ;
Davidow, J ;
Salter, MW .
SCIENCE, 1998, 279 (5355) :1363-1367
[37]   ENHANCED SUSCEPTIBILITY OF AUDIOGENIC-SEIZURES IN FYN-KINASE DEFICIENT MICE [J].
MIYAKAWA, T ;
YAGI, T ;
TANIGUCHI, M ;
MATSUURA, H ;
TATEISHI, K ;
NIKI, H .
MOLECULAR BRAIN RESEARCH, 1995, 28 (02) :349-352
[38]   Fyn-kinase as a determinant of ethanol sensitivity: Relation to NMDA-receptor function [J].
Miyakawa, T ;
Yagi, T ;
Kitazawa, H ;
Yasuda, M ;
Kawai, N ;
Tsuboi, K ;
Niki, H .
SCIENCE, 1997, 278 (5338) :698-701
[39]   Brain-derived neurotrophic factor regulates the expression of AMPA receptor proteins in neocortical neurons [J].
Narisawa-Saito, M ;
Carnahan, J ;
Araki, K ;
Yamaguchi, T ;
Nawa, H .
NEUROSCIENCE, 1999, 88 (04) :1009-1014
[40]  
OBrien RJ, 1997, J NEUROSCI, V17, P7339