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Nat Commun. 2016 Mar 15;7:10997. doi: 10.1038/ncomms10997.

Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments.

Author information

1
Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
2
Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France.
3
Division of Immunology, Transplantation and Infectious Diseases, San Rafaele Scientific Institute, 20132 Milan, Italy.
4
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8002, USA.
5
National Jewish Health and University of Colorado, Denver, Colorado 80206, USA.
6
Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
7
Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.

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.

PMID:
26975831
PMCID:
PMC4796365
DOI:
10.1038/ncomms10997
[Indexed for MEDLINE]
Free PMC Article

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