Ledeen Robert W, Wu Gusheng
Department of Neurology and Neurosciences, New Jersey Medical School-UMDNJ, MSB H506, 185 So. Orange Avenue, Newark, NJ 07103, USA.
Ann N Y Acad Sci. 2007 Mar;1099:494-506. doi: 10.1196/annals.1387.057.
Whereas sodium-calcium exchangers (NCXs) have long been recognized as plasma membrane constituents that serve to maintain homeostatic concentrations of Ca2+ in the cytoplasm, they were recently shown to also occur in the nuclear envelope (NE) of neural and other cells where they function to regulate nuclear Ca2+. A unique feature of NCXs in the NE is their high-affinity binding to GM1 ganglioside, this association being required for optimal exchanger activity. The NCX-GM1 complex occurs in the inner membrane of the NE and transfers Ca2+ from the nucleoplasm to the NE lumen. In neuronal cells, nuclear GM1 levels are low prior to differentiation but increase rapidly as axonal outgrowth progresses. Cells from genetically altered mice lacking GM1 have limited ability to regulate nuclear Ca2+, and the mice themselves showed similar deficit as seen in their high susceptibility to kainite-induced seizures. These are attenuated by LIGA-20, a derivative of GM1 that enters the nuclear membrane and restores nuclear NCX activity to normal level.
虽然钠钙交换体（NCXs）长期以来一直被认为是质膜的组成成分，其作用是维持细胞质中Ca2+的稳态浓度，但最近研究表明，它们也存在于神经细胞和其他细胞的核膜（NE）中，在那里它们起到调节核Ca2+的作用。NE中NCXs的一个独特特征是它们与GM1神经节苷脂具有高亲和力结合，这种结合是交换体最佳活性所必需的。NCX-GM1复合物存在于NE的内膜中，并将Ca2+从核质转移到NE腔中。在神经元细胞中，分化前核GM1水平较低，但随着轴突生长的进行，其水平迅速升高。来自缺乏GM1的基因改造小鼠的细胞调节核Ca2+的能力有限，这些小鼠本身也表现出类似的缺陷，如对红藻氨酸诱导的癫痫高度敏感。GM1的衍生物LIGA-20可减轻这些症状，LIGA-20可进入核膜并将核NCX活性恢复到正常水平。
