斯坦福大学医学院Tsuruta等人发现一种脂质激酶能够引导电压门控钙通道（voltage-gated calcium channel）的退化，从而使得神经元免受钙过量产生的致命影响。这项研究结果发布在2009年10月19日的Journal of Cell Biology上。
在细胞信号传导中，钙是一个重要的参与者，但其在高水平的时候同样也有严重的毒性。神经细胞已经进化出自己的方式避免钙大量进入细胞。一种限制钙进入的方式是移除细胞表面的管家（gatekeepers），钙通道。
神经细胞指导该过程的机制在临床上具有重要意义，该过程紊乱会产生一些严重的问题，比如中风，帕金森氏症和阿尔茨海默病。
在对CaV1.2通道的绑定对象进行蛋白质组扫描后，Tsuruta等人首次筛选出了一种脂质激酶PIKfyve，其能够产生PI(3,5)P2，促进核内体（endosomes）到溶酶体（lysosomes）的成熟。
研究人员猜想，PIKfyve可能引导CaV1.2的退化。他们使用谷氨酸盐兴奋模拟兴奋性压迫，结果表明，CaV1.2是内在化的，且与PIKfyve相关，能在溶酶体中退化。当研究人员抑制PIKfyve 和PI(3,5)P2的水平时，细胞表面出现了过多的通道，这使得神经细胞容易凋亡。
这项研究阐述了神经的自我保护机制，同时表明，现有的钙通道阻滞药物可能使病人免遭神经组织退化紊乱相关疾病的影响。（生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Cell Biology, Vol. 187, No. 2, 279-294 doi:10.1083/jcb.200903028
PIKfyve regulates CaV1.2 degradation and prevents excitotoxic cell death
Fuminori Tsuruta, Eric M. Green, Matthieu Rousset, and Ricardo E. Dolmetsch
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305
Voltage-gated Ca2+ channels (VGCCs) play a key role in neuronal signaling but can also contribute to cellular dysfunction and death under pathological conditions such as stroke and neurodegenerative diseases. We report that activation of N-methyl-D-aspartic acid receptors causes internalization and degradation of CaV1.2 channels, resulting in decreased Ca2+ entry and reduced toxicity. CaV1.2 internalization and degradation requires binding to phosphatidylinositol 3-phosphate 5-kinase (PIKfyve), a lipid kinase which generates phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P2) and regulates endosome and lysosome function. Sustained activation of glutamate receptors recruits PIKfyve to CaV1.2 channels, increases cellular levels of PtdIns(3,5)P2, and promotes targeting of CaV1.2 to lysosomes. Knockdown of PIKfyve prevents CaV1.2 degradation and increases neuronal susceptibility to excitotoxicity. These experiments identify a novel mechanism by which neurons are protected from excitotoxicity and provide a possible explanation for neuronal death in diseases caused by mutations that affect PtdIns(3,5)P2 regulation.
