Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice
Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice
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DOI：
10.1073/pnas.0702275104
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发表时间：
2007-10-30
影响因子：
11.1
通讯作者：
Weisman, Lois S.
中科院分区：
文献类型：
--
作者：
Zhang, Yanling;Zolov, Sergey N.;Weisman, Lois S.
信号脂质磷脂酰肌醇3，5-二磷酸（PI（3，5）P-2）可能在多种信号通路中发挥作用。在这里，我们报告的表征缺乏Vac 14，PI（3，S）P-2合成的调节小鼠突变体。突变小鼠表现出大规模的神经变性，特别是在中脑和外周感觉神经元。受影响的神经元的细胞体空泡化，并且在应该存在神经元的区域中存在明显的空隙。在培养的神经元和成纤维细胞中发现了类似的空泡。选择性膜运输途径，特别是内体到TGN的逆行运输是有缺陷的。该报告，沿着最近关于图4中具有无效突变的小鼠的报告，提出了意想不到的发现，即管家脂质PI（3，5）P-2对于神经细胞的存活至关重要。
The signaling lipid, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P-2), likely functions in multiple signaling pathways. Here, we report the characterization of a mouse mutant lacking Vac14, a regulator of PI(3,S)P-2 synthesis. The mutant mice exhibit massive neurodegeneration, particularly in the midbrain and in peripheral sensory neurons. Cell bodies of affected neurons are vacuolated, and apparently empty spaces are present in areas where neurons should be present. Similar vacuoles are found in cultured neurons and fibroblasts. Selective membrane trafficking pathways, especially endosome-to-TGN retrograde trafficking, are defective. This report, along with a recent report on a mouse with a null mutation in Fig4, presents the unexpected finding that the housekeeping lipid, PI(3,5)P-2, is critical for the survival of neural cells.