Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Dev Biol. 2010 Aug 1;344(1):94-106. doi: 10.1016/j.ydbio.2010.04.025. Epub 2010 May 7.
Ena/VASP proteins mediate the effects of guidance cues on the actin cytoskeleton. The single C. elegans homolog of the Ena/VASP family of proteins, UNC-34, is required for the migrations of cells and growth cones. Here we show that unc-34 mutant alleles also interact genetically with Wnt mutants to reveal a role for unc-34 in the establishment of neuronal polarity along the C. elegans anterior-posterior axis. Our mutant analysis shows that eliminating UNC-34 function results in neuronal migration and polarity phenotypes that are enhanced at higher temperatures, revealing a heat-sensitive process that is normally masked by the presence of UNC-34. Finally, we show that the UNC-34 protein is expressed broadly and accumulates in axons and at the apical junctions of epithelial cells. While most mutants lacked detectable UNC-34, three unc-34 mutants that contained missense mutations in the EVH1 domain produced full-length UNC-34 that failed to localize to apical junctions and axons, supporting the role for the EVH1 domain in localizing Ena/VASP family members.
Ena/VASP 蛋白介导导向线索对肌动蛋白细胞骨架的影响。秀丽隐杆线虫 Ena/VASP 蛋白家族的单一同源物 UNC-34，对于细胞和生长锥的迁移是必需的。在这里，我们表明 unc-34 突变等位基因也与 Wnt 突变体在遗传上相互作用，揭示了 unc-34 在秀丽隐杆线虫前后轴上神经元极性建立中的作用。我们的突变分析表明，消除 UNC-34 功能会导致神经元迁移和极性表型，这些表型在较高温度下增强，揭示了一个通常被 UNC-34 存在掩盖的热敏过程。最后，我们表明 UNC-34 蛋白广泛表达，并在轴突和上皮细胞的顶端连接处积累。虽然大多数突变体缺乏可检测到的 UNC-34，但在 EVH1 结构域中含有错义突变的三个 unc-34 突变体产生全长 UNC-34，未能定位于顶端连接处和轴突，支持 EVH1 结构域在定位 Ena/VASP 家族成员中的作用。
