Institute for Anatomy & Cell Biology, Ulm University, Albert-Einstein Allee 11, 89081 Ulm, Germany.
Cell Tissue Res. 2012 Oct;350(1):13-26. doi: 10.1007/s00441-012-1463-z. Epub 2012 Jul 10.
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.
动力蛋白激活蛋白 p150(Glued)亚基由 DCTN1 基因编码,是负责运动神经元逆行轴突运输的动力蛋白-动力蛋白激活蛋白复合马达蛋白的一部分。p150 亚基是神经退行性疾病的候选基因,特别是运动神经元和锥体外系疾病。微管结合辅助因子被认为参与微管的生物发生和降解,因此有助于微管功能的多样性和调节。酵母双杂交筛选用于 dynactin p150(Glued)的潜在相互作用蛋白已揭示了微管折叠辅助因子 B (TBCB)。我们分析了这些蛋白质的相互作用,并研究了该复合物对细胞系和原代海马神经元体外微管网络的影响。我们特别关注神经元形态和突触发生。两种蛋白质的过表达或 TBCB 的单独耗尽都不会改变微管网络和/或神经元形态。运输分子 dynactin 和微管调节因子 TBCB 的相互作用的证明被认为对几种细胞机制有影响。已经发现 TBCB 的表达水平对微管网络和神经元形态只有细微的影响。然而,TBCB 的过表达导致 p150 向微管网络的定位减少,这可能导致该蛋白复合物的功能调节。