Eukaryotic migration is important in embryogenesis and the immune response, and inappropriate cell migration contributes to pathogenesis, as in metastatic cancer, for example.[m]
Migrating cells extend a protrusion in the direction of motion, and the protrusion attaches to the substratum on which the cell is migrating. In the dynamic, cyclical process that permits migration, protrusion-adhesion is followed by a contraction that pulls the cell body forward towards the adherent-protrusion. Simultaneously, attachments at the rear of the cell are released.
The dynamic migration cycle is initiated in response to binding of chemotactic signals to cellular receptors. Ligand-binding stimuli are transmitted to the intracellular cytoskeleton, triggering polymerization of actin and extension of cellular protrusions (pseudopodia, microvilli). Adhesive complexes are necessary for traction, and collect at the front of the protrusion, tethering it to the substratum. Subsequently, actomyosin filaments contract, dragging the cell body towards the protrusion, while adhesive connections release at the rear of the cell, retracting the tail.
Vinculin is an actin-binding protein that suppresses cell migration by stabilizing focal adhesions. The recently determined crystal structure of vinculin has revealed intramolecular interactions between the head and tail domains which negatively regulate ligand binding. It is likely that different conformational states, with varying affinity for proteins such as talin, alpha-actinin, Arp2/3 or paxillin, contribute to vinculin function not only at focal adhesions but also at cell-cell junctions and in the regulation of signaling pathways leading to apoptosis. [PubMed]
Cdc42 is required for polarizing the leading process in neuronal precursors, the effector complex Par6-Par3-aPKC only regulates the orientation of protrusion. Consistent with in vitro studies, Rac generates localized protrusions in vivo, but is not required for overall polarity. The authors further demonstrate the involvement of PIP3 signaling in the direction and magnitude of protrusion formation, as well as the role of actomyosin contractility in the coordination of spreading and forward advance. Finally, the kinase domain of the receptor tyrosine kinase ErbB4 also appears to be essential for the migration of neuronal precursors. [PubMed]
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