Assembly of filopodia by the formin FRL2 (FMNL3).
Assembly of filopodia by the formin FRL2 (FMNL3).
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DOI：
10.1002/cm.20485
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发表时间：
2010-12
期刊：
影响因子：
2.9
通讯作者：
Higgs, Henry N.
中科院分区：
文献类型：
--
作者：
Harris, Elizabeth S.;Gauvin, Timothy J.;Heimsath, Ernest G.;Higgs, Henry N.
肌动蛋白依赖的指状突起，如丝状伪足和微绒毛广泛存在于真核生物中，但其组装机制知之甚少。丝状伪足的组装需要至少三个肌动蛋白的生化活动：肌动蛋白丝成核，延长肌动蛋白丝伸长，肌动蛋白丝成束。这些活性由几种哺乳动物的FRL蛋白共享，包括mDia 2，FRL 1（也称为FMNL 1）和FRL 2（FMNL 3）。在本文中，我们比较的能力，从这三个formins的结构，以诱导丝状伪足。FRL 2和mDia 2两者的FH 1-FH 2构建体在多种细胞类型中刺激有效的丝状伪足组装，并且在丝状伪足尖端强烈富集。相反，FRL 1 FH 1-FH 2缺乏这种活性，尽管具有类似的生物化学活性并且与FRL 2高度同源。FRL 1和FRL 2之间的嵌合FH 1-FH 2实验表明，虽然需要FH 1和FH 2，但FH 1结构域支持丝状伪足组装，但只有FRL 2的FH 2结构域允许这种活性。损害FRL 2的倒刺末端结合能力的突变废除了丝状伪足组装。FRL 2刺激丝状伪足组装的能力不被额外的结构域（GBD、DID、DAD）改变，但在全长构建体中显著降低，表明FRL 2受到抑制性调节。这些数据表明，FRL 2的FH 2结构域具有FRL 1不具有的特性，使其能够产生丝状伪足。
Actin-dependent finger-like protrusions such as filopodia and microvilli are widespread in eukaryotes, but their assembly mechanisms are poorly understood. Filopodia assembly requires at least three biochemical activities on actin: actin filament nucleation, prolonged actin filament elongation, and actin filament bundling. These activities are shared by several mammalian formin proteins, including mDia2, FRL1 (also called FMNL1), and FRL2 (FMNL3). In this paper, we compare the abilities of constructs from these three formins to induce filopodia. FH1-FH2 constructs of both FRL2 and mDia2 stimulate potent filopodia assembly in multiple cell types, and enrich strongly at filopodia tips. In contrast, FRL1 FH1-FH2 lacks this activity, despite possessing similar biochemical activities and being highly homologous to FRL2. Chimeric FH1-FH2 experiments between FRL1 and FRL2 show that, while both an FH1 and an FH2 are needed, either FH1 domain supports filopodia assembly but only FRL2’s FH2 domain allows this activity. A mutation that compromises FRL2’s barbed end binding ability abolishes filopodia assembly. FRL2’s ability to stimulate filopodia assembly is not altered by additional domains (GBD, DID, DAD), but is significantly reduced in the full-length construct, suggesting that FRL2 is subject to inhibitory regulation. The data suggest that the FH2 domain of FRL2 possesses properties not shared by FRL1 that allow it to generate filopodia.
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DIA1和IQGAP1在细胞迁移和吞噬杯形成中相互作用。
影响因子：
7.8
作者：
Brandt, Dominique T.;Marion, Sabrina;Griffiths, Gareth;Watanabe, Takashi;Kaibuchi, Kozo;Grosse, Robert
通讯作者：
Grosse, Robert
影响因子：
2.9
作者：
GUAN, KL;DIXON, JE
通讯作者：
DIXON, JE
影响因子：
3.3
作者：
Higgs, HN;Peterson, KJ
通讯作者：
Peterson, KJ
影响因子：
4.8
作者：
Han, Yanyan;Eppinger, Elfriede;Krackhardt, Angela M.
通讯作者：
Krackhardt, Angela M.
DOI：
10.1073/pnas.0602443103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Bohil, Aparna B.;Robertson, Brian W.;Cheney, Richard E.
通讯作者：
Cheney, Richard E.