title: Fascin Regulates Nuclear Movement and Deformation in Migrating Cells.
abstract: Fascin is an F-actin-bundling protein shown to stabilize filopodia and regulate adhesion dynamics in migrating cells, and its expression is correlated with poor prognosis and increased metastatic potential in a number of cancers. Here, we identified the nuclear envelope protein nesprin-2 as a binding partner for fascin in a range of cell types in vitro and in vivo. Nesprin-2 interacts with fascin through a direct, F-actin-independent interaction, and this binding is distinct and separable from a role for fascin within filopodia at the cell periphery. Moreover, disrupting the interaction between fascin and nesprin-2 C-terminal domain leads to specific defects in F-actin coupling to the nuclear envelope, nuclear movement, and the ability of cells to deform their nucleus to invade through confined spaces. Together, our results uncover a role for fascin that operates independently of filopodia assembly to promote efficient cell migration and invasion.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London SE1 1UL, UK.
authors.forename: Asier
authors.initials: A
authors.lastname: Jayo
authors.affiliation: London Centre for Nanotechnology, University College London, London WC1H 0AH, UK.
authors.forename: Majid
authors.initials: M
authors.lastname: Malboubi
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Antoku
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Wakam
authors.initials: W
authors.lastname: Chang
authors.affiliation: Division of Asthma, Allergy & Lung Biology, King's College London, 5th Floor Tower Wing, Guy's Hospital Campus, London SE1 1UL, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Ortiz-Zapater
authors.affiliation: Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Groen
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London SE1 1UL, UK.
authors.forename: Karin
authors.initials: K
authors.lastname: Pfisterer
authors.affiliation: Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Tootle
authors.affiliation: London Centre for Nanotechnology, University College London, London WC1H 0AH, UK; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charras
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London SE1 1UL, UK. Electronic address: maddy.parsons@kcl.ac.uk.
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009369:Neoplasms / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000502:physiology*
chemical_list: D000199:Actins; D002352:Carrier Proteins; C502658:FSCN1 protein, human; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485904:SYNE2 protein, human