The role of C. elegans Ena/VASP homolog UNC-34 in neuronal polarity and motility.

The role of C. elegans Ena/VASP homolog UNC-34 in neuronal polarity and motility.
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DOI:
10.1016/j.ydbio.2010.04.025
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发表时间:
2010-08-01
影响因子:
2.7
通讯作者:
Garriga, Gian
Garriga, Gian
中科院分区:
生物学3区
文献类型:
--
作者:
Fleming, Tinya;Chien, Shih-Chieh;Vanderzalm, Pamela J.;Dell, Megan;Gavin, Megan K.;Forrester, Wayne C.;Garriga, Gian

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Ena/VASP蛋白介导的肌动蛋白细胞骨架上的指导线索的影响。唯一的C。ENA/VASP蛋白家族的线虫同源物,ENA-34,是细胞和生长锥迁移所必需的。在这里,我们发现unc-34突变等位基因也与Wnt突变体的遗传相互作用,揭示了unc-34在沿着C. elegans anterior-posterior轴。我们的突变体分析表明,消除β-34功能会导致神经元迁移和极性表型在较高温度下增强,揭示了通常被β-34掩盖的热敏过程。最后,我们发现,在轴突和上皮细胞的顶端连接处广泛表达和积累的α-34蛋白。虽然大多数突变体缺乏可检测的ENA-34,但在EVH 1结构域中含有错义突变的三个unc-34突变体产生了未能定位于顶端连接和轴突的全长ENA-34,支持EVH 1结构域在定位Ena/VASP家族成员中的作用。
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 lack 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.
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