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

Hawa-Racine Thiam, Pablo Vargas, Nicolas Carpi, Carolina Lage Crespo, Matthew Raab, Emmanuel Terriac, Megan C. King, Jordan Jacobelli, Arthur S. Alberts, Theresia Stradal, Ana-Maria Lennon-Dumenil () and Matthieu Piel ()
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Hawa-Racine Thiam: Institut Curie, PSL Research University, CNRS, UMR 144
Pablo Vargas: Institut Curie, PSL Research University, CNRS, UMR 144
Nicolas Carpi: Institut Curie, PSL Research University, CNRS, UMR 144
Carolina Lage Crespo: Transplantation and Infectious Diseases, San Rafaele Scientific Institute
Matthew Raab: Institut Curie, PSL Research University, CNRS, UMR 144
Emmanuel Terriac: Institut Curie, PSL Research University, CNRS, UMR 144
Megan C. King: Yale School of Medicine
Jordan Jacobelli: National Jewish Health and University of Colorado
Arthur S. Alberts: Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute
Theresia Stradal: Helmholtz Centre for Infection Research
Ana-Maria Lennon-Dumenil: Institut Curie, PSL Research University, INSERM U932
Matthieu Piel: Institut Curie, PSL Research University, CNRS, UMR 144

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10997

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