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Nesprin‐2 accumulates at the front of the nucleus during confined cell migration
Author(s) -
Davidson Patricia M,
Battistella Aude,
Déjardin Théophile,
Betz Timo,
Plastino Julie,
Borghi Nicolas,
Cadot Bruno,
Sykes Cécile
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949910
Subject(s) - marie curie , curie , curie temperature , art history , humanities , physics , philosophy , art , condensed matter physics , european union , ferromagnetism , business , economic policy
The mechanisms by which cells exert forces on their nuclei to migrate through openings smaller than the nuclear diameter remain unclear. We use CRISPR/Cas9 to fluorescently label nesprin‐2 giant, which links the cytoskeleton to the nuclear interior. We demonstrate that nesprin‐2 accumulates at the front of the nucleus during nuclear deformation through narrow constrictions, independently of the nuclear lamina. We find that nesprins are mobile at time scales similar to the accumulation. Using artificial constructs, we show that the actin‐binding domain of nesprin‐2 is necessary and sufficient for this accumulation. Actin filaments are organized in a barrel structure around the nucleus in the direction of movement. Using two‐photon ablation and cytoskeleton‐inhibiting drugs, we demonstrate an actomyosin‐dependent pulling force on the nucleus from the front of the cell. The elastic recoil upon ablation is dampened when nesprins are reduced at the nuclear envelope. We thus show that actin redistributes nesprin‐2 giant toward the front of the nucleus and contributes to pulling the nucleus through narrow constrictions, in concert with myosin.