Loss of Arp2/3 induces an NF-κB-dependent, nonautonomous effect on chemotactic signaling
| Autor: | Ian J. Davis, Albert S. Baldwin, James E. Bear, Sreeja B. Asokan, Jeremy M. Simon, Elizabeth M. Haynes, Gary L. Johnson, Norman E. Sharpless, Congying Wu |
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| Rok vydání: | 2013 |
| Předmět: |
Arp2/3 complex
macromolecular substances MAP Kinase Kinase Kinase 3 Biology Actin-Related Protein 2-3 Complex Cell Line 03 medical and health sciences 0302 clinical medicine Epidermal growth factor Osmotic Pressure Report Humans Cytoskeleton Actin Research Articles 030304 developmental biology 0303 health sciences Chemotaxis NF-kappa B Cell migration Cell Biology Actin cytoskeleton Cell biology Actin Cytoskeleton HEK293 Cells Gene Expression Regulation biology.protein biological phenomena cell phenomena and immunity Signal transduction Carrier Proteins 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | A decrease in Arp2/3 levels results in an NF-κB–dependent increase in the expression of several secreted factors, resulting in nonautonomous effects on chemotaxis. Arp2/3-branched actin is critical for cytoskeletal dynamics and cell migration. However, perturbations and diseases affecting this network have phenotypes that cannot be fully explained by cell-autonomous effects. In this paper, we report nonautonomous effects of Arp2/3 depletion. We show that, upon Arp2/3 depletion, the expression of numerous genes encoding secreted factors, including chemokines, growth factors, and matrix metalloproteases, was increased, a signature resembling the senescence-associated secretory phenotype. These factors affected epidermal growth factor chemotaxis in a nonautonomous way, resolving the recent contradictions about the role of Arp2/3 in chemotaxis. We demonstrate that these genes were activated by nuclear factor κB via a CCM2–MEKK3 pathway that has been implicated in hyperosmotic stress signaling. Consistent with this, Arp2/3-depleted cells showed misregulation of volume control and reduced actin in the submembranous cortex. The defects in osmotic signaling in the Arp2/3-depleted cells can be rescued by hypoosmotic treatment. Thus, perturbations of Arp2/3 have nonautonomous effects that should be considered when evaluating experimental manipulations and diseases affecting the Arp2/3-actin cytoskeleton. |
| Databáze: | OpenAIRE |
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