Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.

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, whil...

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Main Authors: Chunxiang Sun, Carol Forster, Fumihiko Nakamura, Michael Glogauer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3808352?pdf=render
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author Chunxiang Sun
Carol Forster
Fumihiko Nakamura
Michael Glogauer
author_facet Chunxiang Sun
Carol Forster
Fumihiko Nakamura
Michael Glogauer
author_sort Chunxiang Sun
collection DOAJ
description 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.
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spelling doaj.art-da8f5c7c94054093a64c184e626307db2022-12-21T18:28:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7900910.1371/journal.pone.0079009Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.Chunxiang SunCarol ForsterFumihiko NakamuraMichael GlogauerFilamin-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.http://europepmc.org/articles/PMC3808352?pdf=render
spellingShingle Chunxiang Sun
Carol Forster
Fumihiko Nakamura
Michael Glogauer
Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
PLoS ONE
title Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
title_full Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
title_fullStr Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
title_full_unstemmed Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
title_short Filamin-A regulates neutrophil uropod retraction through RhoA during chemotaxis.
title_sort filamin a regulates neutrophil uropod retraction through rhoa during chemotaxis
url http://europepmc.org/articles/PMC3808352?pdf=render
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AT fumihikonakamura filaminaregulatesneutrophiluropodretractionthroughrhoaduringchemotaxis
AT michaelglogauer filaminaregulatesneutrophiluropodretractionthroughrhoaduringchemotaxis