Inhibitory effect of several sphingolipid metabolites on calcineurin
Inhibitory effect of several sphingolipid metabolites on calcineurin
复制标题
几种鞘脂代谢物对钙调神经磷酸酶的抑制作用
DOI：
10.1016/j.neulet.2018.03.010
复制
发表时间：
2018
影响因子：
2.5
通讯作者：
Maekawa Shohei
中科院分区：
文献类型：
--
作者：
Maruyama Yoko;Ueno Satoko;Morita Mitsuhiro;Hayashi Fumio;Maekawa Shohei
神经元具有发达的膜微域，称为“筏”，可恢复为耐洗涤剂的膜微域部分(DRM)。NAP-22是神经元DRM的主要蛋白质组分之一。在以前的研究中，我们发现DRM来源的NAP-22与神经节苷脂结合，以及神经节苷脂对钙调蛋白调节的磷酸酶--钙调神经磷酸酶(CaN)的抑制作用。考虑到CaN在神经元中的重要作用，识别CaN的其他细胞调控因子可能是了解神经元功能的分子背景的很好线索。在本研究中，我们筛选了几种膜脂衍生分子对CaN活性的影响，发现鞘氨醇和一些鞘氨醇衍生的代谢物，如鞘氨醇磷胆碱、半乳糖鞘氨醇和葡萄糖鞘氨醇，通过与钙调蛋白的相互作用而对CaN产生抑制作用。
Neurons have well-developed membrane microdomains called “rafts” that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function. In this study, we screened the effect of several membrane lipid-derived molecules on the CaN activity and found sphingosine and some sphingosine-derived metabolites such as sphingosylphosphorylcholine, galactosylsphingosine (psychosine), and glucosylsphingosine, have inhibitory effect on CaN through the interaction with calmodulin.