一个突触前磷酸化信号枢纽，用于持久的动态平衡可塑性。

A presynaptic phosphosignaling hub for lasting homeostatic plasticity.

机构信息

Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, Bonn, Germany; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.

Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, Bonn, Germany.

出版信息

Cell Rep. 2022 Apr 19;39(3):110696. doi: 10.1016/j.celrep.2022.110696.

DOI:10.1016/j.celrep.2022.110696

PMID:35443170

Abstract

Stable function of networks requires that synapses adapt their strength to levels of neuronal activity, and failure to do so results in cognitive disorders. How such homeostatic regulation may be implemented in mammalian synapses remains poorly understood. Here we show that the phosphorylation status of several positions of the active-zone (AZ) protein RIM1 are relevant for synaptic glutamate release. Position RIMS1045 is necessary and sufficient for expression of silencing-induced homeostatic plasticity and is kept phosphorylated by serine arginine protein kinase 2 (SRPK2). SRPK2-induced upscaling of synaptic release leads to additional RIM1 nanoclusters and docked vesicles at the AZ and is not observed in the absence of RIM1 and occluded by RIM. Our data suggest that SRPK2 and RIM1 represent a presynaptic phosphosignaling hub that is involved in the homeostatic balance of synaptic coupling of neuronal networks.

摘要

网络的稳定功能要求突触根据神经元活动水平来调整其强度，如果不能做到这一点，就会导致认知障碍。哺乳动物突触中这种同源调节是如何实现的，目前仍知之甚少。本文中，作者表示，活性区（AZ）蛋白 RIM1 的几个位置的磷酸化状态与突触谷氨酸释放有关。位置 RIMS1045 对于诱导沉默的同源性可塑性表达是必需且充分的，并由丝氨酸精氨酸蛋白激酶 2（SRPK2）保持磷酸化。由 SRPK2 诱导的突触释放的上调会导致 AZ 处的 RIM1 纳米簇和停靠囊泡增加，如果没有 RIM1，则不会观察到这种情况，并且会被 RIM 阻断。这些数据表明，SRPK2 和 RIM1 代表一个参与神经元网络突触偶联的同源平衡的突触磷酸信号中枢。