Integrators of the cytoskeleton that stabilize microtubules
Integrators of the cytoskeleton that stabilize microtubules
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DOI：
10.1016/s0092-8674(00)81017-x
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发表时间：
1999-07-23
期刊：
影响因子：
64.5
通讯作者：
Fuchs, E
中科院分区：
文献类型：
--
作者：
Yang, YM;Bauer, C;Fuchs, E
感觉神经变性发生在BPAG 1缺陷的小鼠中，BPAG 1是编码能够将神经元中间丝锚定到肌动蛋白细胞骨架的细胞骨架连接蛋白的基因。虽然BPAG 1敲除小鼠不能锚定神经丝（NF），但BPAG 1/NF敲除小鼠在没有NF的情况下仍然退化。我们报告了一种新的神经剪接形式，缺乏肌动蛋白结合域，而是结合和稳定微管。这种相互作用在功能上是重要的;在小鼠和体外，缺乏BPAG 1的神经元显示轴突运输缺陷的短，无序和不稳定的微管。具有讽刺意味的是，BPAG 1神经亚型代表微管相关蛋白，当缺乏时会导致毁灭性的后果。此外，BPAG 1可以在功能上解释长距离运输所需的轴突微管的非凡稳定性。它的异构体连接所有三个细胞骨架网络，一个功能显然是神经元存活的核心。
Sensory neurodegeneration occurs in mice defective in BPAG1, a gene encoding cytoskeletal linker proteins capable of anchoring neuronal intermediate filaments to actin cytoskeleton. While BPAG1 null mice fail to anchor neurofilaments (NFs), BPAG1/NF null mice still degenerate in the absence of NFs. We report a novel neural splice form that lacks the actin-binding domain and instead binds and stabilizes microtubules. This interaction is functionally important; in mice and in vitro, neurons lacking BPAG1 display short, disorganized, and unstable microtubules defective in axonal transport. Ironically, BPAG1 neural isoforms represent microtubule-associated proteins that when absent lead to devastating consequences. Moreover, BPAG1 can functionally account for the extraordinary stability of axonal microtubules necessary for transport over long distances. Its isoforms interconnect all three cytoskeletal networks, a feature apparently central to neuronal survival.