Chen Shi-Yuan, Liu Ke-Fang, Tan Shu-Yi, Chen Xiao-Shan, Li Hui-Dong, Li Jing-Jing, Zhou Jian-Wen, Yang Li, Long Cheng
School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
School of Life Sciences, Guangzhou University, Guangzhou 510006, PR China.
Brain Res. 2023 May 1;1806:148313. doi: 10.1016/j.brainres.2023.148313. Epub 2023 Mar 4.
The fate of proteins is determined by the addition of various forms of polyubiquitin during ubiquitin-mediated proteasomal degradation. Cylindromatosis (CYLD), a K63-specific deubiquitinase, is enriched in postsynaptic density fractions of the rodent central nervous system (CNS), but the synaptic role of CYLD in the CNS is poorly understand. Here we show that CYLD deficiency (Cyld) results in reduced intrinsic hippocampal neuronal firing, a decrease in the frequency of spontaneous excitatory postsynaptic currents and a decrease in the amplitude of field excitatory postsynaptic potentials. Moreover, Cyld hippocampus shows downregulated levels of presynaptic vesicular glutamate transporter 1 (vGlut1) and upregulated levels of postsynaptic GluA1, a subunit of the AMPA receptor, together with an altered paired-pulse ratio (PPR). We also found increased activation of astrocytes and microglia in the hippocampus of Cyld mice. The present study suggests a critical role for CYLD in mediating hippocampal neuronal and synaptic activity.
在泛素介导的蛋白酶体降解过程中，蛋白质的命运由各种形式的多聚泛素的添加所决定。圆柱瘤蛋白（CYLD）是一种特异性作用于K63的去泛素化酶，在啮齿动物中枢神经系统（CNS）的突触后致密部分高度富集，但CYLD在中枢神经系统中的突触作用仍知之甚少。在此我们表明，CYLD缺陷（Cyld）会导致海马神经元内在放电减少、自发性兴奋性突触后电流频率降低以及场兴奋性突触后电位幅度减小。此外，Cyld海马体中突触前囊泡谷氨酸转运体1（vGlut1）水平下调，AMPA受体亚基突触后GluA1水平上调，同时配对脉冲比率（PPR）改变。我们还发现Cyld小鼠海马体中星形胶质细胞和小胶质细胞的激活增加。本研究表明CYLD在介导海马神经元和突触活动中起关键作用。
