Tight Coupling Between Nucleus and Cell Migration through the Perinuclear Actin Cap

Abstract

Eukaryotic cells alternate between episodes of fast and persistent movements and “hesitation” episodes of low speed and low persistence. Unlike the well-understood tumbling dynamics in E. Coli, the molecular mechanism that controls the dynamic changes in morphology, speed, and persistence of eukaryotic migratory cells remains unclear. Here, we show that the movement of the interphase nucleus during random cell migration switches intermittently between two distinct modes - rotation and translocation - that follows with high fidelity the sequential rounded and elongated morphologies of the nucleus and the cell, respectively. Nuclear rotation and translocation respectively mediate the stop-and-go motion of the cell through the dynamic formation and dissolution of the contractile perinuclear actin cap, which is dynamically coupled to the nuclear lamina and the nuclear envelope through LINC protein complexes. A persistent cell movement driven by the actin cap and accompanied by actin cap-mediated nuclear translocation, is stopped following actin cap disruption, which in turn allows for the cell to repolarize thanks to dynein for its next persistent move thanks to dynein-mediated nuclear rotation.