Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, South Korea.
Department of Biology, Molecular Cellular Biology Program, Dartmouth College, Hanover, NH, 03755, USA.
Sci Rep. 2017 Jan 31;7:41620. doi: 10.1038/srep41620.
The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in concert, stabilizing neural polarity and generating action potentials. In AP-2 silenced axons polarity is established, however there is a failure to establish action potential firing. Consequently, this impairs activity-driven Ca influx and exocytosis at nerve terminals. In contrast, removal of AP-2 from older neurons does not impair axonal growth or signaling and synaptic function. Our data reveal that AP-2 has important roles in functional axogenesis by proper extension of axon as well as the formation of AIS during the early step of neurodevelopment.
神经网络的复杂性和多样性需要调节轴突的伸长和分支，以及神经元之间突触的形成。在本研究中，我们探讨了 AP-2（一种关键的内吞衔接蛋白复合物）在大鼠海马神经元发育中的作用。我们发现，在发育早期失去 AP-2 会导致轴突延伸受损，轴突起始段（AIS）成熟失败。通常情况下，AIS 协同完成两项任务，稳定神经极性并产生动作电位。在 AP-2 沉默的轴突中，极性得以建立，但无法建立动作电位发放。因此，这会损害神经末梢的活性驱动 Ca 内流和胞吐作用。相比之下，从较老的神经元中去除 AP-2 不会损害轴突生长或信号转导以及突触功能。我们的数据表明，AP-2 通过适当的轴突延伸以及在神经发育的早期步骤中 AIS 的形成，在功能性轴突发生中具有重要作用。
