A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons
A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons
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DOI：
10.1038/ncb1139
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发表时间：
2004-07-01
影响因子：
21.3
通讯作者：
Tsai, LH
中科院分区：
文献类型：
--
作者：
Nguyen, MD;Shu, TZ;Tsai, LH
细胞骨架通过维持轴突和树突的稳定性来控制中枢神经系统（CNS）神经元的结构和存活。尽管神经丝（nf）在这些结构中构成了主要的细胞骨架网络，但亚基融入神经丝的机制仍然是一个谜。本文报道了中性曲霉核分布分子NudE的哺乳动物同源物NUDEL，它对NF的组装、运输和神经元的完整性至关重要。NUDEL通过与NF轻亚基（NF- l）的直接相互作用促进NF的聚合。RNA干扰（RNAi）在神经母细胞瘤细胞系、原代皮质神经元或出生后小鼠大脑中敲低NUDEL可破坏NF-L的稳定并改变nf的稳态。这导致NF异常和形态改变，使人联想到神经变性。此外，在神经变性小鼠模型中，NUDEL水平的变化与疾病进展和NF缺陷相关。因此，NUDEL通过调节NF组装有助于中枢神经系统神经元的完整性。
The cytoskeleton controls the architecture and survival of central nervous system (CNS) neurons by maintaining the stability of axons and dendrites. Although neurofilaments (NFs) constitute the main cytoskeletal network in these structures, the mechanism that underlies subunit incorporation into filaments remains a mystery. Here we report that NUDEL, a mammalian homologue of the Aspergillus nidulans nuclear distribution molecule NudE, is important for NF assembly, transport and neuronal integrity. NUDEL facilitates the polymerization of NFs through a direct interaction with the NF light subunit (NF-L). Knockdown of NUDEL by RNA interference (RNAi) in a neuroblastoma cell line, primary cortical neurons or post-natal mouse brain destabilizes NF-L and alters the homeostasis of NFs. This results in NF abnormalities and morphological changes reminiscent of neurodegeneration. Furthermore, variations in levels of NUDEL correlate with disease progression and NF defects in a mouse model of neurodegeneration. Thus, NUDEL contributes to the integrity of CNS neurons by regulating NF assembly.