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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Singh RK,Liao W,Tracey-White D,Recchi C,Tolmachova T,Rankin SM,Hume AN,Seabra MC

doi

10.1242/jcs.100438

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

1652-6

issue

Pt 7

eissn

0021-9533

issn

1477-9137

pii

jcs.100438

journal_volume

125

pub_type

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