Loeb Jeffrey A
Department of Neurology and The Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Neurocytol. 2003 Jun-Sep;32(5-8):649-64. doi: 10.1023/B:NEUR.0000020640.84708.35.
Synaptic activity in the form of neurotransmitter release and postsynaptic depolarization is a prime motive force that guides synaptic development throughout the nervous system. The molecular basis of how synaptic activity is converted into structural changes that build and maintain synapses is a key question that has recently become focused on regulatory factors that act on tyrosine kinase receptors on both sides of the synaptic interface. The neuregulins are such a family of growth and differentiation factors that exist as both membrane-bound and soluble forms through alternatively splicing. Neuregulin functions to promote the local expression of acetylcholine receptors at neuromuscular synapses and therefore has the potential to strengthen specific synaptic connections. Recent evidence suggests that synaptic activity at the neuromuscular junction is coupled to presynaptic neuregulin release through an indirect mechanism acting through the postsynaptic expression of neurotrophic factors. At early stages of development, this could potentiate the stability of more active synapses. Later in development, heparin-binding forms of neuregulin accumulate to high levels in the synaptic basal lamina through the developmentally programmed expression of heparan sulfate proteoglycans, thus providing a sustained source of neuregulin to the most active synapses.
以神经递质释放和突触后去极化形式存在的突触活动是指导整个神经系统突触发育的主要动力。突触活动如何转化为构建和维持突触的结构变化的分子基础是一个关键问题，最近已聚焦于作用于突触界面两侧酪氨酸激酶受体的调节因子。神经调节蛋白是这样一类生长和分化因子家族，通过可变剪接以膜结合和可溶性两种形式存在。神经调节蛋白的功能是促进神经肌肉突触处乙酰胆碱受体的局部表达，因此具有增强特定突触连接的潜力。最近的证据表明，神经肌肉接头处的突触活动通过一种间接机制与突触前神经调节蛋白的释放相偶联，该间接机制通过神经营养因子的突触后表达起作用。在发育早期，这可能增强更活跃突触的稳定性。在发育后期，神经调节蛋白的肝素结合形式通过硫酸乙酰肝素蛋白聚糖的发育程序性表达在突触基膜中积累到高水平，从而为最活跃的突触提供持续的神经调节蛋白来源。
