Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 85, 20246 Hamburg, Germany.
J Biol Chem. 2010 Sep 10;285(37):28959-67. doi: 10.1074/jbc.M110.114835. Epub 2010 Jul 6.
Recognition molecules and neurotrophins play important roles during development and maintenance of nervous system functions. In this study, we provide evidence that the neural cell adhesion molecule (NCAM) and the neurotrophin receptor TrkB directly interact via sequences in their intracellular domains. Stimulation of TrkB by brain-derived neurotrophic factor leads to tyrosine phosphorylation of NCAM at position 734. Mutation of this tyrosine to phenylalanine completely abolishes tyrosine phosphorylation of NCAM by TrkB. Moreover, the knockdown of TrkB in hippocampal neurons leads to a reduction of NCAM-induced neurite outgrowth. Transfection of NCAM-deficient hippocampal neurons with mutated NCAM carrying an exchange of tyrosine by phenylalanine at position 734 leads to promotion of NCAM-induced neurite outgrowth in comparison with that observed after transfection with wild-type NCAM, whereas a reduction of neurite outgrowth was observed after transfection with mutated NCAM, which carries an exchange of tyrosine by glutamate that mimics the phosphorylated tyrosine. Our observations indicate a functional relationship between TrkB and NCAM.
识别分子和神经营养因子在神经系统功能的发育和维持中起着重要作用。在这项研究中，我们提供了证据表明，神经细胞粘附分子（NCAM）和神经营养因子受体 TrkB 通过其细胞内结构域中的序列直接相互作用。脑源性神经营养因子刺激 TrkB 导致 NCAM 在位置 734 处的酪氨酸磷酸化。该酪氨酸突变为苯丙氨酸可完全消除 TrkB 对 NCAM 的酪氨酸磷酸化。此外，在海马神经元中敲低 TrkB 会导致 NCAM 诱导的神经突生长减少。与转染野生型 NCAM 相比，将位置 734 处的酪氨酸突变为苯丙氨酸的突变型 NCAM 转染缺乏 NCAM 的海马神经元可促进 NCAM 诱导的神经突生长，而转染模拟磷酸化酪氨酸的谷氨酸取代的突变型 NCAM 则会导致神经突生长减少。我们的观察结果表明 TrkB 和 NCAM 之间存在功能关系。
