Wu Xiandeng, Shen Zeyu, Zhang Mingjie
School of Life Sciences, Southern University of Science and Technology, Shenzhen, China; email:
Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Annu Rev Neurosci. 2025 Jul;48(1):149-168. doi: 10.1146/annurev-neuro-112723-040159. Epub 2025 Feb 21.
The synapse is polarized and highly compartmentalized on both its pre- and postsynaptic sides. The compartmentalization of synaptic vesicles, as well as vesicle releasing and recycling machineries, allows neurotransmitters to be released with precisely controlled timing, speed, and amplitude. The compartmentalized and clustered organization of neurotransmitter receptors and their downstream signaling enzymes allows neuronal signals to be properly received and amplified. Synaptic adhesion molecules also form clustered assemblies to align pre- and postsynaptic subcompartments for synaptic formation, stability, and transmission. Recent studies indicate that such synaptic and subsynaptic compartmentalized organizations are formed via phase separation. This review discusses how such condensed subsynaptic compartments may form and function in the context of synapse formation and plasticity. We discuss how phase separation allows for the formation of multiple distinct condensates on both sides of a synapse and how such condensates communicate with each other. We also highlight how proteins display unique properties in condensed phases compared to the same proteins in dilute solutions.
突触在其突触前和突触后两侧都是极化的且高度分隔的。突触小泡的分隔，以及小泡释放和循环机制，使得神经递质能够以精确控制的时间、速度和幅度释放。神经递质受体及其下游信号酶的分隔式和聚集式组织，使得神经元信号能够被正确接收和放大。突触黏附分子也形成聚集组装体，以使突触前和突触后的亚区对齐，从而实现突触的形成、稳定和传递。最近的研究表明，这种突触和亚突触的分隔式组织是通过相分离形成的。本综述讨论了这种浓缩的亚突触区室在突触形成和可塑性的背景下可能如何形成和发挥功能。我们讨论了相分离如何允许在突触两侧形成多个不同的凝聚物，以及这些凝聚物如何相互通信。我们还强调了与稀溶液中的相同蛋白质相比，蛋白质在凝聚相中如何表现出独特的性质。
