Tubulin-binding cofactor B is a direct interaction partner of the dynactin subunit p150Glued
Tubulin-binding cofactor B is a direct interaction partner of the dynactin subunit p150Glued
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DOI：
10.1007/s00441-012-1463-z
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Liebau, Stefan
中科院分区：
文献类型：
--
作者：
Kuh, Georges F.;Stockmann, Marianne;Liebau, Stefan
动力蛋白p150（Glued）亚基由基因DCTN 1编码，是动力蛋白-动力蛋白运动蛋白复合物的一部分，负责运动神经元中的逆行轴突运输。p150亚基是神经退行性疾病，特别是运动神经元和锥体外系疾病的候选基因。微管蛋白结合辅因子被认为参与微管蛋白的生物合成和降解，因此有助于微管功能的多样性和调节。一个酵母双杂交筛选推定的相互作用蛋白的dynactin p150（Glued）揭示了微管蛋白折叠辅因子B（TBCB）。我们分析了这些蛋白质的相互作用，并研究了这种复合物对体外细胞系和原代海马神经元微管网络的影响。我们特别关注神经元形态和突触发生。这两种蛋白质的过表达或TBCB单独的耗竭不改变微管网络和/或神经元形态。运输分子dynactin和微管蛋白调节因子TBCB的相互作用的演示被认为对几种细胞机制有影响。已发现TBCB表达水平对微管网络和神经元形态仅具有微妙的影响。然而，TBCB的过度表达导致p150在微管网络中的定位减少，这可能导致该蛋白复合物的功能调节。
The dynactin p150(Glued) subunit, encoded by the gene DCTN1, is part of the dynein-dynactin motor protein complex responsible for retrograde axonal transport in motor neurons. The p150 subunit is a candidate gene for neurodegenerative diseases, in particular motor neuron and extrapyramidal diseases. Tubulin-binding cofactors are believed to be involved in tubulin biogenesis and degradation and therefore to contribute to microtubule functional diversity and regulation. A yeast-two-hybrid screen for putative interacting proteins of dynactin p150(Glued) has revealed tubulin-folding cofactor B (TBCB). We analyzed the interaction of these proteins and investigated the impact of this complex on the microtubule network in cell lines and primary hippocampal neurons in vitro. We especially concentrated on neuronal morphology and synaptogenesis. Overexpression of both proteins or depletion of TBCB alone does not alter the microtubule network and/or neuronal morphology. The demonstration of the interaction of the transport molecule dynactin and the tubulin-regulating factor TBCB is thought to have an impact on several cellular mechanisms. TBCB expression levels have been found to have only a subtle influence on the microtubule network and neuronal morphology. However, overexpression of TBCB leads to the decreased localization of p150 to the microtubule network that might result in a functional modulation of this protein complex.