Liu Shumin, Ninan Ipe, Antonova Irina, Battaglia Fortunato, Trinchese Fabrizio, Narasanna Archana, Kolodilov Nikolai, Dauer William, Hawkins Robert D, Arancio Ottavio
Department of Pathology, Columbia University, New York, NY, USA.
EMBO J. 2004 Nov 10;23(22):4506-16. doi: 10.1038/sj.emboj.7600451. Epub 2004 Oct 28.
Wild-type alpha-synuclein, a protein of unknown function, has received much attention because of its involvement in a series of diseases that are known as synucleinopathies. We find that long-lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of alpha-synuclein clusters. Conversely, suppression of alpha-synuclein expression through antisense nucleotide and knockout techniques blocks the potentiation, as well as the glutamate-induced increase in presynaptic functional bouton number. Consistent with these findings, alpha-synuclein introduction into the presynaptic neuron of a pair of monosynaptically connected cells causes a rapid and long-lasting enhancement of synaptic transmission, and rescues the block of potentiation in alpha-synuclein null mouse cultures. Also, we report that the application of nitric oxide (NO) increases the number of alpha-synuclein clusters, and inhibitors of NO-synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number of alpha-synuclein clusters. Thus, alpha-synuclein is involved in synaptic plasticity by augmenting transmitter release from the presynaptic terminal.
野生型α-突触核蛋白是一种功能未知的蛋白质，因其与一系列被称为突触核蛋白病的疾病有关而备受关注。我们发现，培养的海马神经元之间突触传递的长时程增强伴随着α-突触核蛋白簇数量的增加。相反，通过反义核苷酸和基因敲除技术抑制α-突触核蛋白的表达会阻断这种增强作用，以及谷氨酸诱导的突触前功能性终扣数量的增加。与这些发现一致，将α-突触核蛋白导入一对单突触连接细胞的突触前神经元会导致突触传递迅速且持久地增强，并挽救α-突触核蛋白基因敲除小鼠培养物中的增强作用阻断。此外，我们报告一氧化氮（NO）的应用会增加α-突触核蛋白簇的数量，而一氧化氮合酶抑制剂会阻断这种增加，支持NO参与α-突触核蛋白簇数量增加的假说。因此，α-突触核蛋白通过增强突触前终末的递质释放参与突触可塑性。
