Elucidation of the molecular mechanism by which valproic acid affects intracellular membrane traffic

丙戊酸（VPA）是一种广泛使用的抗惊厥药物。最近有报道称，VPA可将iPS重编程的效率提高100倍以上，并且VPA可显著增强神经干细胞移植后后肢功能的恢复。VPA在这些情况下的确切作用机制尚不清楚，尽管它已被证明可以改变多种信号通路。我们一直以裂糖菌为模式生物，研究VPA作用的分子机制。这项研究得出了以下结论。我们对非必需单倍体缺失菌株进行了全基因组筛选，并确认148株缺失菌株对VPA敏感。大多数VPA敏感菌株对另一种脂肪酸丁酸钠不敏感。

Valproic acid (VPA) is widely used as an anticonvulsant drug. More recently, it has been reported that VPA improved the efficiency by more than 100-fold upon iPS reprogramming and the administration of VPA dramatically enhanced the restoration of hind limb function upon transplantation of neural stem cells. The exact mechanisms of action of VPA in these conditions remain unclear, although it has been shown to alter a wide variety of signaling pathways. We have been using Schizosaccharomyces pombe as a model organism to study the molecular mechanisms of VPA action. This study led to the following findings. We performed a genome-wide screen of non-essential haploid deletion strains and confirmed 148 deletion strains to be VPA sensitive. Most of the VPA sensitive strains did not show sensitivity to another aliphatic acid sodium butyrate.