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Fascin Regulates Nuclear Movement and Deformation in Migrating Cells
Journal article   Open access   Peer reviewed

Fascin Regulates Nuclear Movement and Deformation in Migrating Cells

Asier Jayo, Majid Malboubi, Susumu Antoku, Wakam Chang, Elena Ortiz-Zapater, Christopher Groen, Karin Pfisterer, Tina Tootle, Guillaume Charras, Gregg G Gundersen, …
Developmental cell, Vol.38(4), pp.371-383
08/22/2016
DOI: 10.1016/j.devcel.2016.07.021
PMCID: PMC4997957
PMID: 27554857
url
https://doi.org/10.1016/j.devcel.2016.07.021View
Published (Version of record) Open Access

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.
Protein Structure, Tertiary Drosophila Humans Actins - metabolism Nuclear Proteins - metabolism Cell Movement - physiology Nerve Tissue Proteins - metabolism Multiprotein Complexes - metabolism Nuclear Envelope - metabolism Animals Carrier Proteins - metabolism Neoplasm Invasiveness - pathology Cell Line, Tumor Mice Microfilament Proteins - metabolism HeLa Cells Pseudopodia - physiology Neoplasms - pathology 3T3 Cells Protein Binding - physiology

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