title: Fascin promotes filopodia formation independent of its role in actin bundling.
abstract: Fascin is an evolutionarily conserved actin-binding protein that plays a key role in forming filopodia. It is widely thought that this function involves fascin directly bundling actin filaments, which is controlled by an N-terminal regulatory serine residue. In this paper, by studying cellular processes in Drosophila melanogaster that require fascin activity, we identify a regulatory residue within the C-terminal region of the protein (S289). Unexpectedly, although mutation (S289A) of this residue disrupted the actin-bundling capacity of fascin, fascin S289A fully rescued filopodia formation in fascin mutant flies. Live imaging of migrating macrophages in vivo revealed that this mutation restricted the localization of fascin to the distal ends of filopodia. The corresponding mutation of human fascin (S274) similarly affected its interaction with actin and altered filopodia dynamics within carcinoma cells. These data reveal an evolutionarily conserved role for this regulatory region and unveil a function for fascin, uncoupled from actin bundling, at the distal end of filopodia.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, SE1 1UL London, England, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zanet
authors.forename: Asier
authors.initials: A
authors.lastname: Jayo
authors.forename: Serge
authors.initials: S
authors.lastname: Plaza
authors.forename: Tom
authors.initials: T
authors.lastname: Millard
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
authors.forename: Brian
authors.initials: B
authors.lastname: Stramer
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004331:Drosophila melanogaster; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000502:physiology*; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008840:Microfilament Proteins; C020324:fascin; D012694:Serine