| First Author | Zoudilova M | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 19 | Pages | 14318-29 |
| PubMed ID | 20207744 | Mgi Jnum | J:162966 |
| Mgi Id | MGI:4820692 | Doi | 10.1074/jbc.M109.055806 |
| Citation | Zoudilova M, et al. (2010) beta-Arrestins scaffold cofilin with chronophin to direct localized actin filament severing and membrane protrusions downstream of protease-activated receptor-2. J Biol Chem 285(19):14318-29 |
| abstractText | Protease-activated receptor-2 (PAR-2) mediates pro-inflammatory signals in a number of organs, including enhancing leukocyte recruitment to sites of injury and infection. At the cellular level, PAR-2 promotes activation of the actin filament-severing protein cofilin, which is crucial for the reorganization of the actin cytoskeleton and chemotaxis. These responses require the scaffolding functions of beta-arrestins; however, the mechanism by which beta-arrestins spatially regulate cofilin activity and the role of this pathway in primary cells has not been investigated. Here, using size-exclusion chromatography and co-immunoprecipitation, we demonstrate that PAR-2 promotes the formation of a complex containing beta-arrestins, cofilin, and chronophin (CIN) in primary leukocytes and cultured cells. Both association of cofilin with CIN and cell migration are inhibited in leukocytes from beta-arrestin-2(-/-) mice. We show that, in response to PAR-2 activation, beta-arrestins scaffold cofilin with its upstream activator CIN, to facilitate the localized generation of free actin barbed ends, leading to membrane protrusion. These studies suggest that a major role of beta-arrestins in chemotaxis is to spatially regulate cofilin activity to facilitate the formation of a leading edge, and that this pathway may be important for PAR-2-stimulated immune cell migration. |
