Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
Mol Neurobiol. 2022 Sep;59(9):5630-5655. doi: 10.1007/s12035-022-02916-1. Epub 2022 Jun 23.
The ER (endoplasmic reticulum) is a Ca reservoir and the unique protein-synthesizing machinery which is distributed throughout the neuron and composed of multiple different structural domains. One such domain is called EMC (endoplasmic reticulum membrane protein complex), pleiotropic nature in cellular functions. The ER/EMC position inside the neurons unmasks its contribution to synaptic plasticity via regulating various cellular processes from protein synthesis to Ca signaling. Since presynaptic Ca channels and postsynaptic ionotropic receptors are organized into the nanodomains, thus ER can be a crucial player in establishing TMNCs (transsynaptic molecular nanocolumns) to shape efficient neural communications. This review hypothesized that ER is not only involved in stress-mediated neurodegeneration but also axon regrowth, remyelination, neurotransmitter switching, information processing, and regulation of pre- and post-synaptic functions. Thus ER might not only be a protein-synthesizing and quality control machinery but also orchestrates plasticity of plasticity (metaplasticity) within the neuron to execute higher-order brain functions and neural repair.
内质网（endoplasmic reticulum，ER）是钙库和分布于整个神经元的独特蛋白质合成机制，由多个不同的结构域组成。其中一个结构域称为 EMC（内质网膜蛋白复合物），在细胞功能中具有多效性。神经元内 ER/EMC 的位置揭示了其通过调节从蛋白质合成到钙信号等各种细胞过程对突触可塑性的贡献。由于突触前 Ca 通道和突触后离子型受体被组织成纳米域，因此 ER 可以成为建立 TMNCs（跨突触分子纳米柱）以形成有效神经通讯的关键参与者。本综述假设 ER 不仅参与应激介导的神经退行性变，还参与轴突再生、髓鞘形成、神经递质转换、信息处理以及调节突触前和突触后功能。因此，ER 不仅是蛋白质合成和质量控制机制，还协调神经元内可塑性（超可塑性），以执行更高阶的大脑功能和神经修复。
