Forming the cell rear first: breaking cell symmetry to trigger directed cell migration

Abstract

Directed cell migration requires the breaking of cell symmetry to generate a cell front and a cell rear along an axis approximately aligned with the direction of locomotion. In most cell types, regulated actin polymerization promotes initial cell front formation and its subsequent persistent protrusion, whereas myosin II-based forces are required to initially create and then maintain the cell rear. Molecular models for cell migration have focused extensively on cell protrusion, and the breaking of cell symmetry is almost universally portrayed with the cell front forming first. Although data supports this model for cells moving towards chemo-attractants, in the absence of any guidance cue, cell symmetry is broken by the cells constitutively forming the cell rear first. This allows an alternative model for triggering cell migration starting with retraction at the back of the cell. In this model, actomyosin II activity within the cell body and prospective cell rear occurs before a spatial bias in actin polymerization at the cell front. Creating the cell rear first may be a useful tool employed by a wide-range of migrating cell types, particularly when moving away from repellent cues.