Mechanism of filopodia initiation by reorganization of a dendritic network.
Mechanism of filopodia initiation by reorganization of a dendritic network.
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DOI：
10.1083/jcb.200210174
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发表时间：
2003-02-03
期刊：
影响因子：
--
通讯作者：
Borisy GG
中科院分区：
文献类型：
--
作者：
Svitkina TM;Bulanova EA;Chaga OY;Vignjevic DM;Kojima S;Vasiliev JM;Borisy GG
拟足通过其核心的束状肌动蛋白丝的伸长而突出。然而，丝状足起始的机制尚不清楚。利用gfp标记蛋白的活细胞成像和相关的电子显微镜，我们对B16F1黑色素瘤细胞的丝状起始进行了动力学结构分析。丝状束不是由一个特定的成核事件产生的，而是由类似于已建立的丝状体融合的板足树突网络的重组产生的，但发生在单个细丝的水平上。独立有核的片状椭球细丝的亚群被拉长，并逐渐在它们的倒刺末端相互连接，从而形成了我们称之为Λ-precursors的锥形结构。起始的早期标志是gfp -血管扩张剂刺激磷酸化蛋白（GFP-VASP）荧光在前缘逐渐合并成离散的病灶。GFP-VASP病灶与Λ-precursors相关，而Arp2/3与Λ-precursors无关。随后，束蛋白聚集到Λ-precursors的簇状倒刺末端，开始了丝束的形成，并完成了新生丝足的形成。我们提出了丝状伪足起始的趋同伸长模型，规定板足树突网络中的细丝通过将一组分子（包括VASP）结合到它们的刺端来获得特权地位，这些分子保护它们不被盖住，并介导刺端相互关联。
Afilopodium protrudes by elongation of bundled actin filaments in its core. However, the mechanism of filopodia initiation remains unknown. Using live-cell imaging with GFP-tagged proteins and correlative electron microscopy, we performed a kinetic-structural analysis of filopodial initiation in B16F1 melanoma cells. Filopodial bundles arose not by a specific nucleation event, but by reorganization of the lamellipodial dendritic network analogous to fusion of established filopodia but occurring at the level of individual filaments. Subsets of independently nucleated lamellipodial filaments elongated and gradually associated with each other at their barbed ends, leading to formation of cone-shaped structures that we term Λ-precursors. An early marker of initiation was the gradual coalescence of GFP-vasodilator-stimulated phosphoprotein (GFP-VASP) fluorescence at the leading edge into discrete foci. The GFP-VASP foci were associated with Λ-precursors, whereas Arp2/3 was not. Subsequent recruitment of fascin to the clustered barbed ends of Λ-precursors initiated filament bundling and completed formation of the nascent filopodium. We propose a convergent elongation model of filopodia initiation, stipulating that filaments within the lamellipodial dendritic network acquire privileged status by binding a set of molecules (including VASP) to their barbed ends, which protect them from capping and mediate association of barbed ends with each other.
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影响因子：
16.2
作者：
Lanier, LM;Gates, MA;Gertler, FB
通讯作者：
Gertler, FB
影响因子：
3.3
作者：
Katoh, K;Hammar, K;Oldenbourg, R
通讯作者：
Oldenbourg, R
DOI：
10.1073/pnas.96.14.7928
发表时间：
1999-07-06
影响因子：
11.1
作者：
Katoh, K;Hammar, K;Oldenbourg, R
通讯作者：
Oldenbourg, R
影响因子：
21.3
作者：
Berg, JS;Cheney, RE
通讯作者：
Cheney, RE
DOI：
10.1083/jcb.119.5.1219
发表时间：
1992-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lewis AK;Bridgman PC
通讯作者：
Bridgman PC