Random versus directionally persistent cell migration

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Abstract
Directional cell migration is an important feature of cell motility that arises from intrinsic cell directionality or external regulation. The mechanisms that drive this process are being deciphered by identifying the specific factors that promote random versus directionally persistent cell migration. Cells achieve and maintain directionally persistent migration by forming and stabilizing protrusions or lamellipodia at their leading edge. Many processes can affect leading edge formation, and they often depend on local regulation of the Rho family of GTPases. The topography of the extracellular matrix provides an important physical cue that can promote directionally persistent migration, possibly by promoting front–rear polarity with geometrically constrained adhesion formation. The Par (partitioning defective) complex is an important contributor to the formation of the front–rear axis of a migrating cell. The Par complex serves as a nexus at the leading edge, connecting Rho GTPase signalling, centrosome reorientation, microtubule stabilization and membrane trafficking to the regulation of directional persistence during cell migration. At each step of the basic cell motility cycle, localized intracellular signalling and/or membrane trafficking can regulate directionally persistent cell migration by controlling the formation of lateral membrane protrusions. New models are needed to recapitulate the physically and biochemically complex environments through which cells navigate in vivo while confronted with competing guidance cues, to further understand how directed cell migration is achieved.