title: Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments.
abstract: Cell migration has two opposite faces: although necessary for physiological processes such as immune responses, it can also have detrimental effects by enabling metastatic cells to invade new organs. In vivo, migration occurs in complex environments and often requires a high cellular deformability, a property limited by the cell nucleus. Here we show that dendritic cells, the sentinels of the immune system, possess a mechanism to pass through micrometric constrictions. This mechanism is based on a rapid Arp2/3-dependent actin nucleation around the nucleus that disrupts the nuclear lamina, the main structure limiting nuclear deformability. The cells' requirement for Arp2/3 to pass through constrictions can be relieved when nuclear stiffness is decreased by suppressing lamin A/C expression. We propose a new role for Arp2/3 in three-dimensional cell migration, allowing fast-moving cells such as leukocytes to rapidly and efficiently migrate through narrow gaps, a process probably important for their function.
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Hawa-Racine
authors.initials: HR
authors.lastname: Thiam
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.|Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France.
authors.forename: Pablo
authors.identifier: http://orcid.org/0000-0002-6475-494X
authors.initials: P
authors.lastname: Vargas
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carpi
authors.affiliation: Division of Immunology, Transplantation and Infectious Diseases, San Rafaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Carolina Lage
authors.initials: CL
authors.lastname: Crespo
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Matthew
authors.initials: M
authors.lastname: Raab
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Terriac
authors.affiliation: Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8002, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: King
authors.affiliation: National Jewish Health and University of Colorado, Denver, Colorado 80206, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Jacobelli
authors.affiliation: Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Alberts
authors.affiliation: Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors.forename: Theresia
authors.initials: T
authors.lastname: Stradal
authors.affiliation: Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Lennon-Dumenil
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Piel
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D003713:Dendritic Cells; D015151:Immunoblotting; D034904:Lamin Type A / Q000378:metabolism; D051379:Mice; D009504:Neutrophils; D034881:Nuclear Lamina / Q000378:metabolism*; D058105:Polymerization
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D034904:Lamin Type A