ALTERED MICROTUBULE ORGANIZATION IN SMALL-CALIBER AXONS OF MICE LACKING TAU-PROTEIN
ALTERED MICROTUBULE ORGANIZATION IN SMALL-CALIBER AXONS OF MICE LACKING TAU-PROTEIN
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DOI：
10.1038/369488a0
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发表时间：
1994-06-09
期刊：
影响因子：
64.8
通讯作者：
HIROKAWA, N
中科院分区：
文献类型：
--
作者：
HARADA, A;OGUCHI, K;HIROKAWA, N
tau基因编码一种蛋白质（Tau），该蛋白质是主要位于轴突中的主要神经元微管相关蛋白（1-4）。它在体外具有微管结合和微管蛋白聚合活性（3，4），并被认为在轴突微管之间形成短的交叉桥（5，6）。此外，tau转染的非神经元细胞延伸长的轴突样突起，其中形成类似于轴突中的微管束的微管束（6-8）。相反，tau反义寡核苷酸选择性地抑制培养的神经元中的轴突伸长（9，10）。因此，tau被认为是神经元细胞形态发生，特别是轴突伸长和维持所必需的。为了验证这一假设，我们使用基因靶向来产生缺乏tau基因的小鼠。我们发现tau蛋白缺陷小鼠的神经系统在免疫组织学上似乎是正常的。此外，在培养的神经元中，轴突伸长不受影响。但在一些小口径轴突中，微管稳定性降低，微管组织发生显著变化。我们观察到微管相关蛋白1A的增加，这可能会补偿大口径轴突中tau蛋白的功能。我们的研究结果反对tau蛋白在轴突伸长中的作用，但证实了它在某种类型的轴突中对轴突微管的稳定和组织至关重要。
THE tau gene encodes a protein (Tau) that is a major neuronal microtubule-associated protein localized mostly in axons(1-4). It has microtubule-binding and tubulin-polymerizing activity in vitro(3,4) and is thought to make short crossbridges between axonal microtuhules(5,6). Further, tau-transfected non-neuronal cells extend long axon-like processes in which microtubule bundles resembling those in axons are formed(6-8). In contrast, tau antisense oligonucleotides selectively suppress axonal elongation in cultured neurons(9,10). Thus tau is thought to be essential for neuronal cell morphogenesis, especially axonal elongation and maintenance. To test this hypothesis, we used gene targeting to produce mice lacking the tau gene. We show that the nervous system of tau-deficient mice appears to be normal immunohistologically. Furthermore, axonal elongation is not affected in cultured neurons. But in some small-calibre axons, microtubule stability is decreased and microtubule organization is significantly changed. We observed an increase in microtubule-associated protein 1A which may compensate for the functions of tau in large-calibre axons. Our results argue against the suggested role of tau in axonal elongation but confirm that it is crucial in the stabilization and organization of axonal microtubules in a certain type of axon.