GMFβ controls branched actin content and lamellipodial retraction in fibroblasts
| Autor: | James E. Bear, Heath E. Johnson, Sreeja B. Asokan, Samantha J. King, Jason M. Haugh, Elizabeth M. Haynes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Glia Maturation Factor
Indoles Arp2/3 complex macromolecular substances Biology Haptotaxis Actin-Related Protein 2-3 Complex Cell Line 03 medical and health sciences Actin remodeling of neurons Mice 0302 clinical medicine Cell Movement Report Animals Protein Isoforms Pseudopodia Actin Research Articles 030304 developmental biology 0303 health sciences Actin remodeling Cell migration Cell Biology Fibroblasts Actins Cell biology Fibronectins Enzyme Activation biology.protein Lamellipodium 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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