Flightless I is a focal adhesion-associated actin-capping protein that regulates cell migration

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Ibrahim MohammadChristopher A G McCulloch

Abstract

The role of adhesion-associated actin-binding proteins in cell migration is not well defined. In mouse fibroblasts we screened for focal adhesion-associated proteins that were isolated with collagen-coated beads and detected by tandem mass spectrometry. We identified flightless I (FliI) as an actin-binding protein in focal adhesion fractions, which was verified by immunoblotting. By confocal microscopy most FliI was distributed throughout the cytosol and in focal adhesions. By sedimentation assays and in vitro binding assays, we found that FliI associates with actin filaments and actin monomers. Assays using purified proteins showed that FliI inhibits actin polymerization and caps but does not sever actin filaments. Cells with FliI knockdown or cells overexpressing FliI migrated more or less rapidly, respectively, than wild-type controls. Compared with controls, cells with FliI knockdown were less adherent than wild-type cells, exhibited reduced numbers of focal adhesions containing activated β1 integrins and vinculin, and exhibited increased incorporation of actin monomers into nascent filaments at focal adhesions. These data indicate that FliI regulates cell migration through its localization to focal adhesions and its abilit...Continue Reading

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Citations

Aug 13, 2013·Periodontology 2000·Yongqiang WangChristopher A McCulloch
Apr 17, 2015·Molecular Biology of the Cell·Pamma D AroraChristopher A McCulloch
Jan 22, 2013·Communicative & Integrative Biology·Allison J CowinRachael Z Murray
Jun 18, 2016·Small GTPases·Hadir Marei, Angeliki Malliri
Jul 16, 2016·International Journal of Molecular Sciences·Zlatko KopeckiAllison J Cowin
Aug 10, 2018·Molecular Biology of the Cell·P D AroraC A McCulloch
Oct 8, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Vanessa I PintoChristopher A McCulloch
Jul 14, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Masaru MezawaChristopher A McCulloch
Jul 10, 2020·Journal of Cellular Physiology·Kei NakajimaChristopher A McCulloch
May 21, 2020·Molecular Biology of the Cell·P D AroraC A McCulloch
Jun 12, 2013·Cytoskeleton·Shalini NagLeslie D Burtnick
May 14, 2020·Journal of Orthopaedic Surgery and Research·Jessica E JacksonAllison J Cowin
Oct 10, 2020·Frontiers in Molecular Biosciences·Réka PintérBeáta Bugyi
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Xanthe L Strudwick, Allison J Cowin

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