Cambiazo V, González M, Maccioni R B
Laboratory of Cellular and Molecular Biology, Faculty of Sciences, University of Chile, Santiago.
J Neurochem. 1995 Mar;64(3):1288-97. doi: 10.1046/j.1471-4159.1995.64031288.x.
Microtubule-associated proteins (MAPs) play major regulatory roles in the organization and integrity of the cytoskeletal network. Our main interest in this study was the identification and the analysis of structural and functional aspects of Drosophila melanogaster MAPs. A novel MAP with a relative molecular mass of 85 kDa from Drosophila larvae was found associated with taxol-polymerized microtubules. In addition, this protein bound to mammalian tubulin in an overlay assay and coassembled with purified bovine brain tubulin in microtubule sedimentation experiments. The estimated stoichiometry of 85-kDa protein versus tubulin in the polymers was 1:5.3 +/- 0.2 mol/mol. It was shown that the 85-kDa protein bound specifically to an affinity column of Sepharose-beta II-(422-434) tubulin peptide, which contains the sequence of the MAP binding domain on beta II-tubulin. Affinity-purified 85-kDa protein enhanced microtubule assembly in a concentration-dependent manner. This effect was significantly decreased by the presence of the beta II-(422-434) peptide in the assembly assays, thus confirming the specificity of the 85-kDa protein interaction with the C-terminal domain on tubulin. Furthermore, this protein also exhibited a strong affinity for calmodulin, based on affinity chromatographic assays. Monoclonal and polyclonal anti-tau antibodies, including sequence-specific probes that recognize repeated microtubule-binding motifs on tau, MAP-2, and MAP-4 and specific N-terminal sequences of tau, cross-reacted with the 85-kDa protein from Drosophila larvae. These results suggest that tau and Drosophila 85-kDa protein share common functional and structural epitopes. We have named this protein as DMAP-85 for Drosophila MAP.(ABSTRACT TRUNCATED AT 250 WORDS)
微管相关蛋白(MAPs)在细胞骨架网络的组织和完整性中发挥着主要调节作用。我们在这项研究中的主要兴趣在于鉴定和分析黑腹果蝇MAPs的结构和功能方面。发现一种来自果蝇幼虫的相对分子质量为85 kDa的新型MAP与紫杉醇聚合的微管相关。此外,在覆盖分析中该蛋白与哺乳动物微管蛋白结合,并在微管沉降实验中与纯化的牛脑微管蛋白共同组装。聚合物中85 kDa蛋白与微管蛋白的估计化学计量比为1:5.3±0.2摩尔/摩尔。结果表明,85 kDa蛋白特异性结合到琼脂糖-β II-(422 - 434)微管蛋白肽的亲和柱上,该肽包含β II-微管蛋白上MAP结合域的序列。亲和纯化的85 kDa蛋白以浓度依赖的方式增强微管组装。在组装分析中β II-(422 - 434)肽的存在显著降低了这种作用,从而证实了85 kDa蛋白与微管蛋白C末端结构域相互作用的特异性。此外,基于亲和色谱分析,该蛋白对钙调蛋白也表现出很强的亲和力。单克隆和多克隆抗tau抗体,包括识别tau、MAP-2和MAP-4上重复微管结合基序以及tau特异性N末端序列的序列特异性探针,与果蝇幼虫的85 kDa蛋白发生交叉反应。这些结果表明tau和果蝇85 kDa蛋白具有共同的功能和结构表位。我们将这种蛋白命名为果蝇MAP的DMAP-85。(摘要截断于250字)