Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, # 309 Medical Science Bldg, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea.
Mol Brain. 2021 Mar 4;14(1):47. doi: 10.1186/s13041-021-00763-0.
Na(K)/H exchanger 6 (NHE6) on synaptic vesicle (SV) is critical for the presynaptic regulation of quantal size at the glutamatergic synapses by converting the chemical gradient (ΔpH) into membrane potential (Δψ) across the SV membrane. We recently found that NHE6 directly interacts with secretory carrier membrane protein 5 (SCAMP5), and SCAMP5-dependent recruitment of NHE6 to SVs controls the strength of synaptic transmission by modulation of quantal size of glutamate release at rest. It is, however, unknown whether NHE6 recruitment by SCAMP5 plays a role during synaptic plasticity. Here, we found that the number of NHE6-positive presynaptic boutons was significantly increased by the chemical long-term potentiation (cLTP). Since cLTP involves new synapse formation, our results indicated that NHE6 was recruited not only to the existing presynaptic boutons but also to the newly formed presynaptic boutons. Knock down of SCAMP5 completely abrogated the enhancement of NHE6 recruitment by cLTP. Interestingly, despite an increase in the number of NHE6-positive boutons by cLTP, the quantal size of glutamate release at the presynaptic terminals remained unaltered. Together with our recent results, our findings indicate that SCAMP5-dependent recruitment of NHE6 plays a critical role in manifesting presynaptic efficacy not only at rest but also during synaptic plasticity. Since both are autism candidate genes, reduced presynaptic efficacy by interfering with their interaction may underlie the molecular mechanism of synaptic dysfunction observed in autism.
钠离子/氢交换体 6（NHE6）位于突触囊泡（SV）上，对于谷氨酸能突触中量子大小的突触前调节至关重要，可将化学梯度（ΔpH）转化为 SV 膜的膜电位（Δψ）。我们最近发现，NHE6 直接与分泌载体膜蛋白 5（SCAMP5）相互作用，SCAMP5 依赖性募集 NHE6 到 SV 控制着静息时谷氨酸释放的量子大小，从而调节突触传递的强度。然而，SCAMP5 募集 NHE6 是否在突触可塑性中发挥作用尚不清楚。在这里，我们发现化学长时程增强（cLTP）显著增加了 NHE6 阳性突触前末梢的数量。由于 cLTP 涉及新的突触形成，我们的结果表明，NHE6 不仅被募集到现有的突触前末梢，而且还被募集到新形成的突触前末梢。SCAMP5 的敲低完全消除了 cLTP 对 NHE6 募集的增强作用。有趣的是，尽管 cLTP 使 NHE6 阳性末梢的数量增加，但突触前末梢谷氨酸释放的量子大小保持不变。结合我们最近的结果，我们的研究结果表明，SCAMP5 依赖性募集 NHE6 不仅在静息时，而且在突触可塑性过程中，对于表现突触前效能都起着至关重要的作用。由于它们都是自闭症候选基因，干扰它们相互作用可能会导致自闭症中观察到的突触功能障碍的分子机制。
