Linear Arrays of Nuclear Envelope Proteins Harness Retrograde Actin Flow for Nuclear Movement

TLDR

Nuclear positioning is essential for cell polarization, yet the actin‑dependent mechanism that reorients the centrosome during fibroblast migration remains unclear. We discovered that nesprin2G and SUN2 form linear arrays on the nuclear envelope that couple to retrograde dorsal actin cables, and disrupting these proteins or actin blocks nuclear movement and centrosome reorientation, demonstrating that nuclear membrane proteins act as actin‑dependent force transducers.

Abstract

Nuclei move to specific locations to polarize migrating and differentiating cells. Many nuclear movements are microtubule-dependent. However, nuclear movement to reorient the centrosome in migrating fibroblasts occurs through an unknown actin-dependent mechanism. We found that linear arrays of outer (nesprin2G) and inner (SUN2) nuclear membrane proteins assembled on and moved with retrogradely moving dorsal actin cables during nuclear movement in polarizing fibroblasts. Inhibition of nesprin2G, SUN2, or actin prevented nuclear movement and centrosome reorientation. The coupling of actin cables to the nuclear membrane for nuclear movement via specific membrane proteins indicates that, like plasma membrane integrins, nuclear membrane proteins assemble into actin-dependent arrays for force transduction.