Caenorhabditis elegans WASP and Ena/VASP proteins play compensatory roles in morphogenesis and neuronal cell migration
Caenorhabditis elegans WASP and Ena/VASP proteins play compensatory roles in morphogenesis and neuronal cell migration
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DOI：
10.1534/genetics.103.025676
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发表时间：
2004-07-01
期刊：
影响因子：
3.3
通讯作者：
Garriga, G
中科院分区：
文献类型：
--
作者：
Withee, J;Galligan, B;Garriga, G
我们在这里报道了WASP和EnA/Vasp家族蛋白在弓形虫形态发生和神经细胞迁移中的重叠作用。具体地说，这些研究表明，UNC-34/ena在形态发生中的作用只有在WSP-1功能缺失的情况下才被揭示，而WSP-1在神经细胞迁移中的作用只有在UNC-34/ena活性缺失的情况下才被揭示。为了确定在形态发生过程中与UNC-34/ENA平行作用的其他基因，我们利用RNAi馈送方法在UNC-34零突变背景下进行了合成致死的筛选。据我们所知，这是第一个报道的基于RNTAi的遗传交互作用筛查。作为这一筛选的结果，我们鉴定了第二个线虫WASP家族蛋白wve-1，它与SCAR/WAVE蛋白最具同源性。WVE-1功能受损的动物表现出原肠形成缺陷，不能进行适当的形态发生，表现出神经细胞迁移和轴突生长缺陷。在UNC-34/ena或WSP-1突变背景中降低wve-1水平也会导致原肠形成和形态发生缺陷的显着增强。因此，UNC-34/ena、WSP-1和WVE-1在胚胎发育过程中起重叠作用，UNC-34/ena和WSP-1在神经细胞迁移过程中起重叠作用。这些观察表明，WASP和Ena/Vasp蛋白在体内可以相互补偿，并首次证明了Ena/Vasp蛋白在原肠形成和形态发生中的作用。此外，我们的结果提供了WASP家族蛋白在后生动物神经细胞迁移和胞质分裂中的体内作用的第一个例子。
We report here that WASP and Ena/VASP family proteins play overlapping roles in C. elegansmorphogenesis and neuronal cell migration. Specifically, these studies demonstrate that UNC-34/Ena plays a role in morphogenesis that is revealed only in the absence of WSP-1 function and that WSP-1 has a role in neuronal cell migration that is revealed only in the absence of UNC-34/Ena activity. To identify additional genes that act in parallel to unc-34/ena during morphogenesis, we performed a screen for synthetic lethals in an unc-34 null mutant background utilizing an RNAi feeding approach. To our knowledge, this is the first reported RNTAi-based screen for genetic interactors. As a result of this screen, we identified a second C. elegans WASP family protein, wve-1, that is most homologous to SCAR/WAVE proteins. Animals with impaired wve-1 function display defects in gastrulation, fail to undergo proper morphogenesis, and exhibit defects in neuronal cell migrations and axon outgrowth. Reducing wve-1 levels in either unc-34/ena or wsp-1 mutant backgrounds also leads to a significant enhancement of the gastrulation and morphogenesis defects. Thus, unc-34/ena, wsp-1, and wve-1 play overlapping roles during embryogenesis and unc-34/ena and wsp-1 play overlapping roles in neuronal cell migration. These observations show that WASP and Ena/VASP proteins can compensate for each other in vivo and provide the first demonstration of a role for Ena/VASP proteins in gastrulation and morphogenesis. In addition, our results provide the first example of an in vivo role for WASP family proteins in neuronal cell migrations and cytokinesis in metazoans.