A Rac switch regulates random versus directionally persistent cell migration

TLDR

Directional migration rapidly transports cells between points, while random migration enables local exploration. The study investigates how Rac1 activity determines whether cells migrate randomly or persistently in a given direction. High Rac1 activity generates peripheral lamellae that drive random migration, whereas reduced Rac1 shifts cells to directionally persistent movement. This Rac1‑dependent switch operates independently of PI3K signaling and is evident in three‑dimensional cultures, where lower Rac1 levels correlate with rapid directional migration.

Abstract

Directional migration moves cells rapidly between points, whereas random migration allows cells to explore their local environments. We describe a Rac1 mechanism for determining whether cell patterns of migration are intrinsically random or directionally persistent. Rac activity promoted the formation of peripheral lamellae that mediated random migration. Decreasing Rac activity suppressed peripheral lamellae and switched the cell migration patterns of fibroblasts and epithelial cells from random to directionally persistent. In three-dimensional rather than traditional two-dimensional cell culture, cells had a lower level of Rac activity that was associated with rapid, directional migration. In contrast to the directed migration of chemotaxis, this intrinsic directional persistence of migration was not mediated by phosphatidylinositol 3′-kinase lipid signaling. Total Rac1 activity can therefore provide a regulatory switch between patterns of cell migration by a mechanism distinct from chemotaxis.