dc.contributor.author | Carbo, Carla | |
dc.contributor.author | Duerschmied, Daniel | |
dc.contributor.author | Goerge, Tobias | |
dc.contributor.author | Hattori, Hidenori | |
dc.contributor.author | Sakai, Jiro | |
dc.contributor.author | Cifuni, Stephen M. | |
dc.contributor.author | White, Gilbert C. | |
dc.contributor.author | Chrzanowska-Wodnicka, Magdalena | |
dc.contributor.author | Luo, Hongbo | |
dc.contributor.author | Wagner, Denisa D. | |
dc.date.accessioned | 2014-11-05T19:37:36Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Carbo, Carla, Daniel Duerschmied, Tobias Goerge, Hidenori Hattori, Jiro Sakai, Stephen M. Cifuni, Gilbert C. White, Magdalena Chrzanowska-Wodnicka, Hongbo R. Luo, and Denisa D. Wagner. 2010. “Integrin-Independent Role of CalDAG-GEFI in Neutrophil Chemotaxis.” Journal of Leukocyte Biology 88 (2) (April 22): 313–319. doi:10.1189/jlb.0110049. http://dx.doi.org/10.1189/jlb.0110049. | en_US |
dc.identifier.issn | 0741-5400 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:13350264 | |
dc.description.abstract | Chemotaxis and integrin activation are essential processes for neutrophil transmigration in response to injury. CalDAG-GEFI plays a key role in the activation of β1, β2, and β3 integrins in platelets and neutrophils by exchanging a GDP for a GTP on Rap1. Here, we explored the role of CalDAG-GEFI and Rap1b in integrin-independent neutrophil chemotaxis. In a transwell assay, \(CalDAG-GEFI^{−/−}\) neutrophils had a 46% reduction in transmigration compared with WT in response to a low concentration of \(LTB_4\). Visualization of migrating neutrophils in the presence of 10 mM EDTA revealed that \(CalDAG-GEFI^{−/−}\) neutrophils had abnormal chemotactic behavior compared with WT neutrophils, including reduced speed and directionality. Interestingly, \(Rap1b^{−/−}\) neutrophils had a similar phenotype in this assay, suggesting that CalDAG-GEFI may be acting through Rap1b. We investigated whether the deficit in integrin-independent chemotaxis in \(CalDAG-GEFI^{−/−}\) neutrophils could be explained by defective cytoskeleton rearrangement. Indeed, we found that CalDAG-GEFI−/− neutrophils had reduced formation of F-actin pseudopodia after \(LTB_4\) stimulation, suggesting that they have a defect in polarization. Overall, our studies show that CalDAG-GEFI helps regulate neutrophil chemotaxis, independent of its established role in integrin activation, through a mechanism that involves actin cytoskeleton and cellular polarization. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Society for Leukocyte Biology | en_US |
dc.relation.isversionof | doi:10.1189/jlb.0110049 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pubmed/20413728 | en_US |
dash.license | META_ONLY | |
dc.subject | Rap1 | en_US |
dc.subject | adhesion | en_US |
dc.subject | F-actin | en_US |
dc.subject | polarization | en_US |
dc.title | Integrin-Independent Role of CalDAG-GEFI in Neutrophil Chemotaxis | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | Journal of Leukocyte Biology | en_US |
dash.depositing.author | Luo, Hongbo | |
dash.embargo.until | 10000-01-01 | |
dc.identifier.doi | 10.1189/jlb.0110049 | * |
dash.contributor.affiliated | Cifuni, Stephen | |
dash.contributor.affiliated | Luo, Hongbo | |
dash.contributor.affiliated | Wagner, Denisa | |