Cell：保持微管稳定的蛋白Mal3p被发现

生物谷

生物谷报道：细胞是一座“繁华闹市”，高峰期时，载体会携带分子沿微管（microtubules）构成的动力系统传输。微管不断地伸缩，快速适应载体的要求进行组装，但是在传输过程中，微管需要保持稳定状态。来自欧洲分子生物学实验室的研究人员发现一个可以通过与微管薄弱区域——lattice  seam结合而稳定微管的蛋白，并且此蛋白沿着seam形成一个特殊的表面，为运输提供了一种候选轨道。研究结果刊登于本周《Cell》杂志。

    微管蛋白（tubulins）是微管的基本结构，它们聚集在一起形成原纤维（protofilaments），几股原纤维在一起形成一个大的微管蛋白片层。研究人员观察酵母中这些微管蛋白片层组装为微管的方式，发现一种关键蛋白——Mal3p。电镜实验发现Mal3p与微管seam相结合，将微管蛋白片层的两边连接起来形成一个管道。Mal3p蛋白沿seam排列成为一条直线，“焊接”微管，在微管薄弱位点稳定微管。“这是首次发现一种与微管seam特异结合的蛋白，”EMBL研究小组前任带头人Andreas  Hoenger说，“  seam的功能现在仍然未知，其一度被认为是微管网架（microtubule  lattice）临时的、不相关的部分。我们的实验证明它是调节微管稳定性的中心位点。”

    没有Mal3p，微管会变得不稳定，容易解开，Mal3p是微管行为的关键调节者。细胞可以通过控制Mal3p的有无，快速改变微管的收缩状态，这对于快速的灵活的细胞运输非常重要。Mal3p沿微管seam的定位非常关键，因为在微管seam，Mal3p可以在不妨碍沿微丝的动力蛋白运输的情况下提供稳定性。除了稳定功能，Mal3p在运输过程中还发挥更积极的作用。

    EMBL研究小组领导人  Damian  Brunner说：“动力蛋白通过与微管蛋白直接接触，沿微管移动。沿它们运动的载体如同高速公路上的货车。沿seam的一连串Mal3p提供了微丝上的另一条候选轨道，沿这条轨道，特异的动力蛋白可以运动，如同与高速公路并行的铁路。这种双系统使运输更加多样化，更加有效。”

     在酵母研究中得到的关于细胞运输和微管稳定性的新发现，有助于揭示其在人类中的相似过程。Mal3p在进化过程中相当保守，人类结肠癌或神经退行性疾病等都与Mal3p有关。

Figure 1. Mal3p Interactions with Microtubules In Vivo and In Vitro

(A) Confocal images of S. pombe expressing endogenous levels of Mal3p tagged at its carboxyl terminus with GFP via a 22 residue linker. Mal3pLGFP highlights the bundles of dynamic microtubules by associating with the entire set of microtubule lattices. In addition the protein accumulates at distal microtubule plus ends and at plus ends growing along the microtubule bundles.

(B) Schematic model of microtubule arrangements in S. pombe. Microtubules align in antiparallel bundles with their minus ends overlapping around the nucleus, while the growing plus ends (arrowheads) point to cell tips.

(C) Copelleting assay of Mal3p and tubulin. In all preparations Mal3p concentration was kept at 2.5 μM. In the absence of tubulin Mal3p was found in the supernatant only. With increasing tubulin concentration more and more Mal3p was found in the pellet. However, only with approximately nine times more tubulin than Mal3p could saturation be reached, demonstrating that there are far fewer Mal3p-binding sites than tubulin dimers.

(D) Turbidity caused by tubulin polymerization (22 μM/37°C) under increasing Mal3p concentrations measured at λ = 350 nm as a function of time. Compared to the control in the absence of Mal3p, increasing concentrations of Mal3p raised the equilibrium between polymerized and free tubulin toward microtubules. In addition, while the control reached a clear plateau, in the presence of Mal3p microtubule formation appeared to grow slowly for a longer time, indicating that Mal3p kept microtubules from shrinking.

原文出处：

Cell December 29, 2006: 127 (7)

The Schizosaccharomyces pombe EB1 Homolog Mal3p Binds and Stabilizes the Microtubule Lattice Seamp1415
Linda Sandblad, Karl Emanuel Busch, Peter Tittmann, Heinz Gross, Damian Brunner, and Andreas Hoenger
[Summary] [Full Text] [PDF]

相关基因：

SPAC637.07

hypothetical protein [Schizosaccharomyces pombe 972h-]

Other Aliases: SPAC637.07, moe1

Chromosome: I

GeneID: 2543412

EB1

estrogen receptor binding CpG island [Homo sapiens]

GeneID: 9165

This record was replaced with GeneID: 9167

作者简介：

CMCI: Brunner Group

HOENGER Andreas Ph. D.

"study of kinesin and other molecular motors by cryo-electron microscopy"

Group Leader in Structural and Computational Biology (EMBL) since 1998

Postdoctoral research at the Scripps Research Institute, La Jolla and at the Institute of Cell Biology, ETH-Zürich, Switzerland.
PhD 1993 M.E. Müller Institute, Biocenter, University of Basel, Switzerland.