GMFβ controls branched actin content and lamellipodial retraction in fibroblasts.
GMFβ controls branched actin content and lamellipodial retraction in fibroblasts.
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DOI：
10.1083/jcb.201501094
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发表时间：
2015-06-22
期刊：
影响因子：
--
通讯作者：
Bear JE
中科院分区：
文献类型：
--
作者：
Haynes EM;Asokan SB;King SJ;Johnson HE;Haugh JM;Bear JE
GMFβ在体内的主要活性是肌动蛋白分支的分解（而不是抑制Arp2/3的激活），这种活性在板足动力学和向ECM信号的定向迁移中起重要作用。片层基是细胞迁移的重要结构，含有通过Arp2/3复合物成核的支链肌动蛋白。分支肌动蛋白的形成研究相对较好，但对其分解及其如何影响迁移的了解较少。GMF参与了Arp2/3的脱支和抑制Arp2/3的激活。GMFβ是一种普遍存在的GMF异构体，通过缺失或过表达来调节GMFβ会导致板足动力学、分支肌动蛋白含量和迁移的变化。CK-666对Arp2/3的急性药理抑制，结合该复合物的定量活细胞成像，表明GMFβ的消耗降低了分支肌动蛋白的分解速率。这些数据以及诱变研究表明，脱分枝（而不是抑制Arp2/3的激活）是GMFβ在体内的主要活性。此外，GMFβ的缺失或过表达破坏了细胞向纤维连接蛋白梯度定向迁移的能力（趋向性）。这些数据表明GMFβ脱支在支化肌动蛋白调控、板足动力学和定向迁移中起重要作用。
The primary activity of GMFβ in vivo is actin branch disassembly (and not inhibition of Arp2/3 activation), and this activity plays an important role in lamellipodial dynamics and directional migration toward ECM cues. The lamellipodium is an important structure for cell migration containing branched actin nucleated via the Arp2/3 complex. The formation of branched actin is relatively well studied, but less is known about its disassembly and how this influences migration. GMF is implicated in both Arp2/3 debranching and inhibition of Arp2/3 activation. Modulation of GMFβ, a ubiquitous GMF isoform, by depletion or overexpression resulted in changes in lamellipodial dynamics, branched actin content, and migration. Acute pharmacological inhibition of Arp2/3 by CK-666, coupled to quantitative live-cell imaging of the complex, showed that depletion of GMFβ decreased the rate of branched actin disassembly. These data, along with mutagenesis studies, suggest that debranching (not inhibition of Arp2/3 activation) is a primary activity of GMFβ in vivo. Furthermore, depletion or overexpression of GMFβ disrupted the ability of cells to directionally migrate to a gradient of fibronectin (haptotaxis). These data suggest that debranching by GMFβ plays an important role in branched actin regulation, lamellipodial dynamics, and directional migration.
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影响因子：
16.8
作者：
Luan, Qing;Nolen, Brad J.
通讯作者：
Nolen, Brad J.
DOI：
10.1083/jcb.201306032
发表时间：
2013-12-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wu C;Haynes EM;Asokan SB;Simon JM;Sharpless NE;Baldwin AS;Davis IJ;Johnson GL;Bear JE
通讯作者：
Bear JE
DOI：
10.1073/pnas.86.10.3901
发表时间：
1989-05-01
影响因子：
11.1
作者：
LIM, R;MILLER, JF;ZAHEER, A
通讯作者：
ZAHEER, A
DOI：
10.1016/j.cub.2010.03.026
发表时间：
2010-05-11
期刊：
Current biology : CB
影响因子：
--
作者：
Gandhi M;Smith BA;Bovellan M;Paavilainen V;Daugherty-Clarke K;Gelles J;Lappalainen P;Goode BL
通讯作者：
Goode BL
影响因子：
11.8
作者：
Rotty, Jeremy D.;Wu, Congying;Haynes, Elizabeth M.;Suarez, Cristian;Winkelman, Jonathan D.;Johnson, Heath E.;Haugh, Jason M.;Kovar, David R.;Bear, James E.
通讯作者：
Bear, James E.