title: Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment.
abstract: Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
authors.affiliation: Molecular Medicine, National Heart and Lung Institute (NHLI), Imperial College, London, UK.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: Wenjia
authors.initials: W
authors.lastname: Liao
authors.forename: Dhani
authors.initials: D
authors.lastname: Tracey-White
authors.forename: Chiara
authors.initials: C
authors.lastname: Recchi
authors.forename: Tanya
authors.initials: T
authors.lastname: Tolmachova
authors.forename: Sara M
authors.initials: SM
authors.lastname: Rankin
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Hume
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
mesh_terms: D000818:Animals; D002465:Cell Movement; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000075745:rab27 GTP-Binding Proteins; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins