Guidolin Diego, Tortorella Cinzia, Marcoli Manuela, Cervetto Chiara, Maura Guido, Agnati Luigi F
Department of Neuroscience, Section of Anatomy, University of Padova, 35121, Padova, Italy.
Department of Neuroscience, Section of Anatomy, University of Padova, 35121, Padova, Italy.
Neuropharmacology. 2023 Jun 15;231:109509. doi: 10.1016/j.neuropharm.2023.109509. Epub 2023 Mar 17.
It is well known that astrocytes play a significant metabolic role in the nervous tissue, maintaining the homeostasis of the extracellular space and of the blood-brain barrier, and providing trophic support to neurons. In addition, however, evidence exists indicating astrocytes as important elements for brain activity through signaling exchange with neurons. Astrocytes, indeed, can sense synaptic activity and their molecular machinery responds to neurotransmitters released by neurons with cytoplasmic Ca elevations that, in turn, stimulate the release of neuroactive substances (gliotransmitters) influencing nearby neurons. In both cell types the recognition and transduction of this complex pattern of signals is mediated by specific receptors that are also involved in mechanisms tuning the intercellular cross-talk between astrocytes and neurons. Two of these mechanisms are the focus of the present discussion. The first concerns direct receptor-receptor interactions leading to the formation at the cell membrane of multimeric receptor complexes. The cooperativity that emerges in the actions of orthosteric and allosteric ligands of the monomers forming the assembly provides the cell decoding apparatus with sophisticated and flexible dynamics in terms of recognition and signal transduction pathways. A further mechanism of plasticity involving receptors is based on the transfer of elements of the cellular signaling apparatus via extracellular microvesicles acting as protective containers, which can lead to transient changes in the transmitting/decoding capabilities of the target cell. This article is part of the Special Issue on "The receptor-receptor interaction as a new target for therapy".
众所周知，星形胶质细胞在神经组织中发挥着重要的代谢作用，维持细胞外空间和血脑屏障的稳态，并为神经元提供营养支持。然而，除此之外，有证据表明星形胶质细胞通过与神经元的信号交换，是大脑活动的重要组成部分。事实上，星形胶质细胞能够感知突触活动，其分子机制会对神经元释放的神经递质做出反应，导致细胞质钙离子浓度升高，进而刺激影响附近神经元的神经活性物质（胶质递质）的释放。在这两种细胞类型中，这种复杂信号模式的识别和转导是由特定受体介导的，这些受体也参与调节星形胶质细胞和神经元之间细胞间相互作用的机制。本讨论聚焦于其中两种机制。第一种涉及直接的受体 - 受体相互作用，导致在细胞膜上形成多聚体受体复合物。构成该组装体的单体的正构和变构配体作用中出现的协同性，为细胞解码装置在识别和信号转导途径方面提供了复杂而灵活的动力学。另一种涉及受体的可塑性机制基于细胞信号装置元件通过作为保护容器的细胞外微泡进行转移，这可导致靶细胞的传递/解码能力发生瞬时变化。本文是“受体 - 受体相互作用作为治疗新靶点”特刊的一部分。
