SHATI/NAT8L Regulates Neurite Outgrowth Via Microtubule Stabilization
SHATI/NAT8L Regulates Neurite Outgrowth Via Microtubule Stabilization
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DOI：
10.1002/jnr.23273
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发表时间：
2013-12-01
影响因子：
4.2
通讯作者：
Nabeshima, Toshitaka
中科院分区：
文献类型：
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作者：
Toriumi, Kazuya;Ikami, Miki;Nabeshima, Toshitaka
我们以前确定了一个新的分子，SHATI/NAT 8L，它对甲基苯丙胺（METH）诱导的过度运动，敏化和条件性位置偏爱具有抑制作用。然而，SHATI的本地化程度及其功能仅被部分理解。在这项研究中，我们使用FLAG标签的方法来研究SHATI定位。我们发现SHATI在COS 7细胞和皮层原代神经元中表达时定位于微管。在用秋水仙碱处理细胞后，SHATI的这种分布不那么明显，秋水仙碱是一种破坏微管结构的微管蛋白聚合抑制剂。这一发现表明SHATI与微管结构有关。有趣的是，在COS 7细胞中过表达SHATI可以减弱秋水仙素诱导的乙酰化微管减少，表明SHATI在稳定微管中起作用。此外，我们发现，Shati缺失损害神经突起的延伸。在皮层初级神经元中，Shati基因敲除（KO）小鼠的神经突长度和复杂性显著降低。与野生型小鼠相比，Shati-KO小鼠前额叶皮质锥体神经元的树突长度和复杂性也显著降低。这些结果表明，一个新的功能SHATI，这可能是一个新的成员微管相关蛋白家族。(c)2013 Wiley Periodicals，Inc.
We previously identified a new molecule, SHATI/NAT8L, which has an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference. Nevertheless, the extent of SHATI localization and its functions are only partially understood. In this study, we used the FLAG-tag method to investigate SHATI localization. We found that SHATI was localized to microtubules when expressed in COS7 cells and cortical primary neurons. This distribution of SHATI was less apparent after cells were treated with colchicine, a tubulin polymerization inhibitor that disrupts the microtubule structure. This finding suggests that SHATI is associated with microtubule structure. Interestingly, overexpression of SHATI in COS7 cells could attenuate the colchicine-induced decrease in acetylated microtubules, indicating that SHATI plays a role in stabilizing microtubules. Furthermore, we showed that Shati deletion impaired neurite elongation. In cortical primary neurons, neurite length and complexity in Shati-knockout (KO) mice were significantly decreased. In pyramidal neurons in the prefrontal cortex, dendrite length and complexity were also significantly decreased in Shati-KO mice compared with wild-type mice. These results suggest a novel function for SHATI, which may be a new member of the microtubule-associated protein family. (c) 2013 Wiley Periodicals, Inc.