Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Focus Program Translational Neurosciences (FTN), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
J Physiol. 2021 Jan;599(2):471-483. doi: 10.1113/JP276698. Epub 2020 Jul 24.
AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate affinity, conductance and peak open probability. Next we explain how the presence of auxiliary subunits alters temporal precision and integrative properties of synapses by influencing gating kinetics of the receptors. Auxiliary subunits of the TARP and CKAMP family modulate synaptic short-term plasticity by increasing anchoring of AMPARs in synapses and by altering their desensitization kinetics. We then describe how auxiliary subunits of the TARP, CKAMP and CNIH families are involved in Hebbian and homeostatic plasticity, which can be explained by their influence on surface trafficking and synaptic targeting. In conclusion, the series of studies covered in this review show that auxiliary subunits play a pivotal role in controlling information processing in the brain by modulating synaptic computation.
AMPA 型谷氨酸受体 (AMPARs) 是大脑中神经元通讯的关键分子。TARP、CKAMP 和 CNIH 家族等辅助亚基的发现，从根本上改变了我们对 AMPAR 功能如何受到调节的理解。辅助亚基控制大脑中 AMPAR 功能的几乎所有方面。它们影响 AMPAR 的组装、组成、结构、运输、亚细胞定位和门控。这种影响对突触功能有重要意义。在本综述中，我们首先讨论了辅助亚基如何通过调节突触中 AMPAR 的数量和定位以及它们的谷氨酸亲和力、电导和峰值开放概率来影响突触强度。接下来，我们解释了辅助亚基如何通过影响受体的门控动力学来改变突触的时间精度和整合特性。TARP 和 CKAMP 家族的辅助亚基通过增加 AMPAR 在突触中的锚定和改变其脱敏动力学来调节突触的短期可塑性。然后，我们描述了 TARP、CKAMP 和 CNIH 家族的辅助亚基如何参与赫布和动态平衡可塑性，这可以通过它们对表面运输和突触靶向的影响来解释。总之，本综述中涵盖的一系列研究表明，辅助亚基通过调节突触计算在控制大脑中的信息处理方面发挥着关键作用。
