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Actin Accumulates Nesprin-2 at the Front of the Nucleus During Confined Cell Migration

34 Pages Posted: 29 Jul 2019 Sneak Peek Status: Review Complete

See all articles by Patricia Marie Davidson

Patricia Marie Davidson

Sorbonne University - Laboratoire Physico-Chimie Curie

Aude Battistella

Sorbonne University - Laboratoire Physico-Chimie Curie

Theophile Dejardin

Sorbonne University - Laboratoire Physico-Chimie Curie

Timo Betz

Zentrum für Molekularbiologie der Entzündung (ZMBE) - Institute of Cell Biology

Julie Plastino

Sorbonne University - Laboratoire Physico-Chimie Curie

Bruno Cadot

Sorbonne University - Center for Research in Myology

Nicolas Borghi

Université Paris VII Denis Diderot - IJM - Institut Jacques Monod

Cecile Sykes

Sorbonne University - Laboratoire Physico-Chimie Curie

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Abstract

The mechanisms by which cells exert forces on their nuclei to migrate through openings smaller than the nuclear diameter remain unclear. In microfluidic devices, the hourglass shape of the nucleus and its strain patterns as it translocates through narrow constrictions suggest pulling forces. We use CRISPR/Cas9 to label nesprin-2 giant, a protein that links the cytoskeleton to the interior of the nucleus. We demonstrate that nesprin-2 giant accumulates at the front of the nucleus during nuclear deformation through narrow constrictions, independently of the nuclear lamina. We find that nesprins are more mobile than lamin A/C, and hypothesize that nesprin accumulation at the front is a consequence of forward pulling by the cytoskeleton. Using artificial constructs, we show indeed that the actin-binding domain of nesprin-2 is necessary and sufficient to generate this accumulation, and that microtubules are not involved. Actin filaments are organized in a barrel structure around the moving nucleus in the direction of movement. This and estimates of nesprin elongation suggest that actin pulling forces on nesprins are distributed around the deformed nucleus towards the front.

Keywords: actin, nucleus, shape, deformation, migration, cancer, nesprin, lamin, CRISPR, LINC complex

Suggested Citation

Davidson, Patricia Marie and Battistella, Aude and Dejardin, Theophile and Betz, Timo and Plastino, Julie and Cadot, Bruno and Borghi, Nicolas and Sykes, Cecile, Actin Accumulates Nesprin-2 at the Front of the Nucleus During Confined Cell Migration (July 25, 2019). Available at SSRN: https://ssrn.com/abstract=3426657 or http://dx.doi.org/10.2139/ssrn.3426657
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Patricia Marie Davidson (Contact Author)

Sorbonne University - Laboratoire Physico-Chimie Curie ( email )

Paris
France

Aude Battistella

Sorbonne University - Laboratoire Physico-Chimie Curie ( email )

Paris
France

Theophile Dejardin

Sorbonne University - Laboratoire Physico-Chimie Curie

Paris
France

Timo Betz

Zentrum für Molekularbiologie der Entzündung (ZMBE) - Institute of Cell Biology

Münster
Germany

Julie Plastino

Sorbonne University - Laboratoire Physico-Chimie Curie

Paris
France

Bruno Cadot

Sorbonne University - Center for Research in Myology

Paris
France

Nicolas Borghi

Université Paris VII Denis Diderot - IJM - Institut Jacques Monod

2, place Jussieu
Paris, 75005
France

Cecile Sykes

Sorbonne University - Laboratoire Physico-Chimie Curie ( email )

Paris
France

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