The Drosophila microtubule associated protein Futsch is phosphorylated by Shaggy/Zeste-white 3 at an homologous GSK3β phosphorylation site in MAP1B
The Drosophila microtubule associated protein Futsch is phosphorylated by Shaggy/Zeste-white 3 at an homologous GSK3β phosphorylation site in MAP1B
复制标题
DOI：
10.1016/j.mcn.2006.07.004
复制
发表时间：
2006-10-01
影响因子：
3.5
通讯作者：
Gordon-Weeks, Phillip R.
中科院分区：
文献类型：
--
作者：
Goegel, Stefanie;Wakefield, Sarah;Gordon-Weeks, Phillip R.
微管相关蛋白MAP 1B的果蝇同源物由futsch基因座编码。推导的蛋白Futsch的大小约为MAP 1B的两倍，并且在N-和C-末端结构域中显示出高同源性。Futsch的中心部分的特征在于基于37个氨基酸基序的高度重复结构。与MAP 1B一样，Futsch与微管共定位，并且是轴突生长和突触发生期间微管细胞骨架组织所必需的。为了进一步分析Futsch作为MAP 1B样蛋白的功能相关性，我们对保守蛋白结构域进行了分子分析。使用一些抗血清，我们表明，与MAP 1B多聚蛋白，这是裂解产生的重链和轻链，Futsch是作为一个单一的蛋白质表达。MAP 1B的功能部分受酪蛋白激酶2和糖原合成酶激酶3 β（GSK 3 β）介导的磷酸化调节。我们在这里表明，至少有一个GSK 3 β磷酸化位点的MAP 1B是保守的Futsch，这个网站可以磷酸化的GSK 3 β和果蝇同源物，沙吉/Zeste-white 3。为了测试这些发现的功能相关性，我们产生了一些小基因，并测定了它们拯救futsch突变体表型的能力。我们的数据突出了MAP 1B和Futsch之间的一些差异，但表明重要的结构和功能方面是保守的苍蝇和脊椎动物的成员之间的蛋白质家族。(c)2006年爱思唯尔公司All rights reserved.
The Drosophila homologue of the microtubule associated protein MAP1B is encoded by the futsch locus. The deduced protein Futsch is about twice the size of MAP1B and shows high homology in the N- and C-terminal domains. The central part of Futsch is characterized by a highly repetitive structure based on a 37 amino acid motif. Futsch, like MAP1B, colocalizes with microtubules and is necessary for the organization of the microtubule cytoskeleton during axonal growth and synaptogenesis. To further analyze the functional relevance of Futsch as a MAP1B-like protein, we performed a molecular analysis of the conserved protein domains. Using a number of antisera, we show that, unlike the MAP1B polyprotein, which is cleaved to generate a heavy and light chain, Futsch is expressed as a single protein. The function of MAP1B is in part regulated by phosphorylation mediated by kinases that include casein kinase 2 and glycogen synthase kinase 3 beta (GSK3 beta). We show here that at least one GSK3 beta phosphorylation site of MAP1B is conserved in Futsch and that this site can be phospborylated by GSK3 beta and its Drosophila homologue, Shaggy/Zeste-white 3. To test the functional relevance of these findings we generated a number of minigenes and assayed their ability to rescue the phenotype of futsch mutants. Our data highlight some differences between MAP1B and Futsch but demonstrate that important structural and functional aspects are conserved between fly and vertebrate members of this protein family. (c) 2006 Elsevier Inc. All rights reserved.