Lamellipodial versus filopodial mode of the actin nanomachinery: Pivotal role of the filament barbed end
Lamellipodial versus filopodial mode of the actin nanomachinery: Pivotal role of the filament barbed end
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DOI：
10.1016/j.cell.2004.07.019
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发表时间：
2004-08-06
期刊：
影响因子：
64.5
通讯作者：
Borisy, GG
中科院分区：
文献类型：
--
作者：
Mejillano, MR;Kojima, S;Borisy, GG
了解一种特定的细胞类型如何表达肌动蛋白机制的片状或丝状伪足形式对于理解细胞的功能相互作用至关重要。为了确定细胞如何在这些可供选择的“分子硬件”模式中“选择”，我们测试了影响肌动蛋白丝倒刺末端的关键蛋白质的作用。短发夹RNA（shRNA）的帽蛋白（CP）的消耗造成的板状伪足和丝状伪足的爆炸性形成的损失。敲低表型被拯救的CP突变体难治性的shRNA，但不是由另一个有倒钩的末端封端，凝溶胶蛋白，证明该表型是特异性的CID。在EnaNASP缺陷细胞中，CP消耗导致皱褶而不是丝状伪足。我们提出了一个模型选择lamelipodial与filepodial组织中，CP是一个负调节器filepodia的形成和EnaNASP有招聘/激活功能下游的肌动蛋白丝伸长除了其先前建议的anticapping和antibranching活动。
Understanding how a particular cell type expresses the lamellipodial or filopodial form of the actin machinery is essential to understanding a cell's functional interactions. To determine how a cell "chooses" among these alternative modes of "molecular hardware," we tested the role of key proteins that affect actin filament barbed ends. Depletion of capping protein (CP) by short hairpin RNA (shRNA) caused loss of lamellipodia and explosive formation of filopodia. The knockdown phenotype was rescued by a CP mutant refractory to shRNA, but not by another barbed-end capper, gelsolin, demonstrating that the phenotype was specific for CID. In EnaNASP deficient cells, CP depletion resulted in ruffling instead of filopodia. We propose a model for selection of lamellipodial versus filopodial organization in which CP is a negative regulator of filopodia formation and EnaNASP has recruiting/activating functions downstream of actin filament elongation in addition to its previously suggested anticapping and antibranching activities.