Andreska Thomas, Lüningschrör Patrick, Sendtner Michael
Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97080, Wuerzburg, Germany.
Cell Tissue Res. 2020 Oct;382(1):5-14. doi: 10.1007/s00441-020-03224-7. Epub 2020 Jun 15.
Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression.
神经营养因子通过受体酪氨酸激酶发出的信号对于脊椎动物神经系统的发育和功能至关重要。与介导对神经生长因子和神经营养因子-3反应的Trk家族的其他受体酪氨酸激酶相比，TrkB的激活和信号传导表现出显著差异。越来越多的证据表明，TrkB在细胞表面的表达受到高度调控，并决定了神经元对脑源性神经营养因子（BDNF）的敏感性。TrkB的这种易位取决于环磷酸腺苷（cAMP）水平的辅助因子和调节剂、N-糖基化以及受体反式激活。这个过程可以在非常短的时间内发生，由此导致的靶细胞对BDNF敏感性的快速调节可能代表了一种在复杂神经元网络中微调突触可塑性和通讯的机制。本综述聚焦于神经元中那些通过控制TrkB表面表达来调节对BDNF反应性的调节机制。
