Dissecting regulatory networks of filopodia formation in a Drosophila growth cone model.
Dissecting regulatory networks of filopodia formation in a Drosophila growth cone model.
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DOI：
10.1371/journal.pone.0018340
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发表时间：
2011-03-28
期刊：
影响因子：
3.7
通讯作者：
Prokop A
中科院分区：
文献类型：
--
作者：
Gonçalves-Pimentel C;Gombos R;Mihály J;Sánchez-Soriano N;Prokop A
肌动蛋白网络是细胞形状和形态发生的重要结构决定因素。它们通过许多肌动蛋白结合蛋白进行调节。许多这些蛋白质的功能是很好的理解，但很少有人知道他们如何合作，并整合他们的活动在细胞环境中。在这里，我们集中在细胞的肌动蛋白调节器在控制丝状伪足动力学的作用。丝状伪足是针状的肌动蛋白驱动的细胞突起，具有脊椎动物和无脊椎动物中非常保守的特征。然而，现有的丝状伪足形成模型仍然是不完整的和有争议的，从广泛的不同生物和细胞类型拼凑而成。因此，我们使用果蝇胚胎初级神经元作为一个一致的细胞模型来研究丝状伪足的调节。我们的数据为失去功能的加帽蛋白，使不同的Arp 2/3复合物的组件，的ADDAAM和profilin揭示特征的变化，在丝状伪足的数量和长度，提供了一个有前途的起点，研究其功能关系的细胞背景。此外，结果是一致的影响报告各自的脊椎动物同源物，证明了我们的果蝇模型系统的保守性。利用组合遗传学，我们证明了不同类别的核合作丝状伪足的形成。在Arp 2/3或DAAM的情况下，丝状伪足的数量减少，在它们的组合的情况下，丝状伪足被消除，并且在遗传测定中，它们显示出关于丝状伪足形成的强功能相互作用。这两种成核因子在基因上也与enabled相互作用，但不与profilin相互作用。相比之下，enabled显示出与profilin的强遗传相互作用，尽管单独的profilin的损失不影响丝状伪足的数量。我们的遗传数据支持一种模型，其中Arp 2/3和DAAM在丝状伪足形成的共同机制中合作，该机制基本上依赖于启用，并通过在不同步骤中的profilin活性进行调节。
F-actin networks are important structural determinants of cell shape and morphogenesis. They are regulated through a number of actin-binding proteins. The function of many of these proteins is well understood, but very little is known about how they cooperate and integrate their activities in cellular contexts. Here, we have focussed on the cellular roles of actin regulators in controlling filopodial dynamics. Filopodia are needle-shaped, actin-driven cell protrusions with characteristic features that are well conserved amongst vertebrates and invertebrates. However, existing models of filopodia formation are still incomplete and controversial, pieced together from a wide range of different organisms and cell types. Therefore, we used embryonic Drosophila primary neurons as one consistent cellular model to study filopodia regulation. Our data for loss-of-function of capping proteins, enabled, different Arp2/3 complex components, the formin DAAM and profilin reveal characteristic changes in filopodia number and length, providing a promising starting point to study their functional relationships in the cellular context. Furthermore, the results are consistent with effects reported for the respective vertebrate homologues, demonstrating the conserved nature of our Drosophila model system. Using combinatorial genetics, we demonstrate that different classes of nucleators cooperate in filopodia formation. In the absence of Arp2/3 or DAAM filopodia numbers are reduced, in their combined absence filopodia are eliminated, and in genetic assays they display strong functional interactions with regard to filopodia formation. The two nucleators also genetically interact with enabled, but not with profilin. In contrast, enabled shows strong genetic interaction with profilin, although loss of profilin alone does not affect filopodia numbers. Our genetic data support a model in which Arp2/3 and DAAM cooperate in a common mechanism of filopodia formation that essentially depends on enabled, and is regulated through profilin activity at different steps.
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影响因子：
4.6
作者：
Gates, Julie;Mahaffey, James P.;Peifer, Mark
通讯作者：
Peifer, Mark
影响因子：
3.3
作者：
Delalle, I;Pfleger, CM;Hariharan, IK
通讯作者：
Hariharan, IK
影响因子：
10.5
作者：
GERTLER, FB;COMER, AR;HOFFMANN, FM
通讯作者：
HOFFMANN, FM
DOI：
10.1083/jcb.201003014
发表时间：
2010-11-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hansen SD;Mullins RD
通讯作者：
Mullins RD
影响因子：
7.5
作者：
Chesarone MA;Goode BL
通讯作者：
Goode BL