Morimoto T, Ohsawa I, Takamura C, Ishiguro M, Nakamura Y, Kohsaka S
Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo 187-8502, Japan.
J Neurosci. 1998 Nov 15;18(22):9386-93. doi: 10.1523/JNEUROSCI.18-22-09386.1998.
The effect of the secretory form of amyloid precursor protein (sAPP) on synaptic transmission was examined by using developing neuromuscular synapses in Xenopus cell cultures. The frequency of spontaneous postsynaptic currents (SSCs) was reduced by the addition of sAPP, whereas the amplitude of impulse-evoked postsynaptic currents (ESCs) was increased by sAPP. These opposing effects on spontaneous versus evoked release were separated by using the specific domain of APP. The C-terminal fragment of sAPP (CAPP) only reduced SSC frequency and did not affect ESCs. By contrast, the N-terminal fragment of sAPP (NAPP) did not affect SSC frequency but did increase ESC amplitude. The reduction of SSC frequency by sAPP appears to be mediated by activation of potassium channels through a cGMP-dependent pathway, whereas the increase of ESC amplitude is mediated by a different pathway involving activation of protein kinase(s). These results suggest the potential role of sAPP as a modulator of synaptic activity by two specific domains.
通过在非洲爪蟾细胞培养物中利用发育中的神经肌肉突触，研究了淀粉样前体蛋白分泌形式（sAPP）对突触传递的影响。添加sAPP可降低自发突触后电流（SSCs）的频率，而sAPP可增加冲动诱发突触后电流（ESCs）的幅度。通过使用APP的特定结构域，区分了对自发释放与诱发释放的这些相反作用。sAPP的C末端片段（CAPP）仅降低SSC频率，而不影响ESCs。相比之下，sAPP的N末端片段（NAPP）不影响SSC频率，但确实增加了ESC幅度。sAPP对SSC频率的降低似乎是通过cGMP依赖性途径激活钾通道介导的，而ESC幅度的增加是由涉及蛋白激酶激活的不同途径介导的。这些结果表明sAPP作为突触活性调节剂通过两个特定结构域发挥潜在作用。
