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Publication : GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation.

First Author  Fine N Year  2016
Journal  J Cell Biol Volume  215
Issue  1 Pages  107-119
PubMed ID  27738004 Mgi Jnum  J:331757
Mgi Id  MGI:6208115 Doi  10.1083/jcb.201603109
Citation  Fine N, et al. (2016) GEF-H1 is necessary for neutrophil shear stress-induced migration during inflammation. J Cell Biol 215(1):107-119
abstractText  Leukocyte crawling and transendothelial migration (TEM) are potentiated by shear stress caused by blood flow. The mechanism that couples shear stress to migration has not been fully elucidated. We found that mice lacking GEF-H1 (GEF-H1(-/-)), a RhoA-specific guanine nucleotide exchange factor (GEF), displayed limited migration and recruitment of neutrophils into inflamed tissues. GEF-H1(-/-) leukocytes were deficient in in vivo crawling and TEM in the postcapillary venules. We demonstrated that although GEF-H1 deficiency had little impact on the migratory properties of neutrophils under static conditions, shear stress triggered GEF-H1-dependent spreading and crawling of neutrophils and relocalization of GEF-H1 to flotillin-2-rich uropods. Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.
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