Spinophilin regulates the formation and function of dendritic spines
Spinophilin regulates the formation and function of dendritic spines
复制标题
DOI：
10.1073/pnas.97.16.9287
复制
发表时间：
2000-08-01
影响因子：
11.1
通讯作者：
Greengard, P
中科院分区：
文献类型：
--
作者：
Feng, J;Yan, Z;Greengard, P
亲棘蛋白是一种与肌动蛋白和蛋白磷酸酶 - 1相互作用的蛋白质，在树突棘中高度富集。在此，通过使用亲棘蛋白敲除小鼠，我们提供的证据表明亲棘蛋白调节谷氨酸能突触传递和树突形态。在亲棘蛋白敲除小鼠中，蛋白磷酸酶 - 1调节α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）和N - 甲基 - D - 天冬氨酸（NMDA）受体活性的能力降低。与谷氨酸能传递改变一致，亲棘蛋白缺陷小鼠表现出长时程抑制降低，并对红藻氨酸诱导的癫痫发作和神经元凋亡具有抵抗力。此外，亲棘蛋白基因的缺失导致体内发育过程中树突棘密度显著增加以及培养神经元中丝状伪足形成改变。总之，亲棘蛋白似乎是调节树突棘特性所必需的。
Spinophilin, a protein that interacts with actin and protein phosphatase-1, is highly enriched in dendritic spines. Here, through the use of spinophilin knockout mice, we provide evidence that spinophilin modulates both glutamatergic synaptic transmission and dendritic morphology, The ability of protein phosphatase-1 to regulate the activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors was reduced in spinophilin knockout mice. Consistent with altered glutamatergic transmission, spinophilin-deficient mice showed reduced long-term depression and exhibited resistance to kainate-induced seizures and neuronal apoptosis. In addition, deletion of the spinophilin gene caused a marked increase in spine density during development in vivo as well as altered filopodial formation in cultured neurons. In conclusion, spinophilin appears to be required for the regulation of the properties of dendritic spines.