title: Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
abstract: Filamin-A (FLNa) has been shown to be a key cross-linker of actin filaments in the leading edge of a motile melanoma cell line, however its role in neutrophils undergoing chemotaxis is unknown. Using a murine transgenic model in which FLNa is selectively deleted in granulocytes, we report that, while neutrophils lacking FLNa show normal polarization and pseudopod extension, they exhibit obvious defects in uropod retraction. This uropod retraction defect was found to be a direct result of reduced FLNa mediated activation of the small GTPase RhoA and myosin mediated actin contraction in the FLNa null cells. This results in a neutrophil recruitment defect in FLNa null mice. The compensatory increase in FLNb levels that was observed in the FLNa null neutrophils may be sufficient to compensate for the lack of FLNa at the leading edge allowing for normal polarization, however this compensation is unable to regulate RhoA activated tail retraction at the rear of the cell.
authors.affiliation: The Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Sun
authors.forename: Carol
authors.initials: C
authors.lastname: Forster
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
mesh_terms: D000818:Animals; D016764:Cell Polarity; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis; D064448:Filamins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005838:Genotype; D008822:Mice, Transgenic; D009218:Myosins / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D002630:Chemotactic Factors; D064448:Filamins; C529499:FlnA protein, mouse; D009218:Myosins; D020742:rhoA GTP-Binding Protein