Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.
Max Planck Institute for Brain Research, Max von Laue Str. 4, 60438, Frankfurt am Main, Germany.
Cell Mol Life Sci. 2019 Jun;76(11):2133-2169. doi: 10.1007/s00018-019-03068-7. Epub 2019 Apr 1.
To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Their trafficking to, at, and from the synapse, is, therefore, a key mechanism underlying synaptic plasticity. Intensive research over the last 20 years has revealed the increasing importance of interacting proteins, which accompany AMPA receptors throughout their lifetime and help to refine the temporal and spatial modulation of their trafficking and function. In this review, we discuss the current knowledge about the roles of key partners in regulating AMPA receptor trafficking and focus especially on the movement between the intracellular, extrasynaptic, and synaptic pools. We examine their involvement not only in basal synaptic function, but also in Hebbian and homeostatic plasticity. Included in our review are well-established AMPA receptor interactants such as GRIP1 and PICK1, the classical auxiliary subunits TARP and CNIH, and the newest additions to AMPA receptor native complexes.
为了正确传递信息，神经元网络需要不断调整其突触强度以适应外在刺激。这种能力被称为突触可塑性，是其功能的核心，因此受到严格的调控。在谷氨酸能神经元中，突触强度受突触后 AMPA 受体的数量和功能控制，后者介导中枢神经系统中大多数快速兴奋传递。因此，它们在突触处的运输、定位和离开是突触可塑性的关键机制。在过去的 20 年中，密集的研究揭示了相互作用蛋白的重要性不断增加，这些蛋白伴随着 AMPA 受体的整个生命周期，并有助于精细调节其运输和功能的时空调制。在这篇综述中，我们讨论了关于调节 AMPA 受体运输的关键伙伴的作用的现有知识，并特别关注它们在细胞内、细胞外突触和突触之间的运动。我们不仅研究了它们在基础突触功能中的作用，还研究了赫布和动态平衡可塑性。我们的综述包括 GRIP1 和 PICK1 等已确立的 AMPA 受体相互作用蛋白、经典辅助亚基 TARP 和 CNIH 以及 AMPA 受体天然复合物的最新成员。
