School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
Neuroscientist. 2020 Oct-Dec;26(5-6):415-437. doi: 10.1177/1073858420921117. Epub 2020 May 23.
The efficient targeting of ionotropic receptors to postsynaptic sites is essential for the function of chemical excitatory and inhibitory synapses, constituting the majority of synapses in the brain. A growing body of evidence indicates that cell adhesion molecules (CAMs), which accumulate at synapses at the earliest stages of synaptogenesis, are critical for this process. A diverse variety of CAMs assemble into complexes with glutamate and GABA receptors and regulate the targeting of these receptors to the cell surface and synapses. Presynaptically localized CAMs provide an additional level of regulation, sending a trans-synaptic signal that can regulate synaptic strength at the level of receptor trafficking. Apart from controlling the numbers of receptors present at postsynaptic sites, CAMs can also influence synaptic strength by modulating the conductivity of single receptor channels. CAMs thus act to maintain basal synaptic transmission and are essential for many forms of activity dependent synaptic plasticity. These activities of CAMs may underlie the association between CAM gene mutations and synaptic pathology and represent fundamental mechanisms by which synaptic strength is dynamically tuned at both excitatory and inhibitory synapses.
离子型受体在突触后部位的有效靶向对于化学兴奋性和抑制性突触的功能至关重要，这些突触构成了大脑中大多数突触。越来越多的证据表明，细胞粘附分子（CAMs）在突触发生的最早阶段就聚集在突触处，对于这个过程至关重要。多种 CAM 组装成与谷氨酸和 GABA 受体的复合物，并调节这些受体在细胞表面和突触上的靶向。定位于突触前的 CAM 提供了额外的调节水平，发送跨突触信号，可以在受体运输水平上调节突触强度。CAM 不仅可以通过调节单个受体通道的导电性来控制突触后部位存在的受体数量，还可以影响突触强度。因此，CAM 起到维持基础突触传递的作用，是许多形式的活动依赖性突触可塑性所必需的。CAM 的这些活性可能是 CAM 基因突变与突触病理学之间关联的基础，并且代表了在兴奋性和抑制性突触上动态调节突触强度的基本机制。
