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Eur J Cell Biol. 2017 Sep;96(6):553-566. doi: 10.1016/j.ejcb.2017.05.004. Epub 2017 May 27.

Filamin A promotes efficient migration and phagocytosis of neutrophil-like HL-60 cells.

Author information

1
Department of Cell Biology (Anatomy III), Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany.
2
Department of Cardiovascular Physiology and Pathophysiology, Walter Brendel Centre of Experimental Medicine, Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany.
3
Department of Cell Biology (Anatomy III), Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany. Electronic address: amueller@lrz.uni-muenchen.de.

Abstract

The primary defense machinery to combat inflammation involves neutrophil granulocytes which in order to execute their functions rely on the efficiency of different cellular mechanisms including adhesion, spreading, migration in different environments, and phagocytosis. These functions require an accurately regulated actin network as well as the activation and adjustment of various signaling pathways. Mammalian filamins (FLNs) comprise three highly homologous large actin-binding proteins that are obvious candidates to control these processes as FLNs have been described to play a role in migration, spreading and adhesion in a variety of different cell types. The present study analyzed the role of filamin A (FLNa) in human neutrophil-like HL-60 cells. We found a strong enrichment of FLNa at the uropod of migrating neutrophils, and show that deficiency of FLNa caused a decrease in speed of migration both in 2D and 3D that is accompanied by a reduced activation of myosin-II. In addition, we show that FLNa plays a role in neutrophil phagocytosis. We also identified a hitherto unknown interaction of FLNa with coronin 1A that is mediated by FLNa repeats 9-18. FLNa deficiency had no or only minor effects on cell adhesion and spreading. In summary, deficiency of FLNa in human neutrophil-like HL-60 cells resulted in a surprisingly subtle phenotype. Our data indicate that FLNa is not essential for the regulation of mechanical properties during migration, but contributes to motility in a modulatory manner probably through its action at the uropod.

KEYWORDS:

Adhesion; Chemotaxis; Coronin; FLNa; Migration; Phagocytosis

PMID:
28595776
DOI:
10.1016/j.ejcb.2017.05.004
[Indexed for MEDLINE]

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