Our evolving view of cell motility

Various cells scattered throughout the eukaryotic tree crawl across surfaces or through three-dimensional environments in order to hunt prey, evade predators and find mates. Evidence now indicates that cell crawling is not a single behavior, but rather a collection of processes, driven by different molecular mechanisms. We seek to understanding regulation and evolution of these mechanisms by first narrowly defining mechanical modes of locomotion, and then identifying phenotypic and molecular markers of each. The best studied mode of cell migration is the adhesion-based migration of highly adherent animal cells, including fibroblasts and epithelial cells, a mode limited to cells of the animal lineage. In contrast, a mode we refer to as “alpha-motility” is widely dispersed among eukaryotic phyla and is characterized by dynamic, actin-filled pseudopods and weak adhesion to external substrates. We are currently defining gene complements required for each mode, and using the resulting data to predict crawling motility in new species. We use this approach to predict alpha-motility in the amphibian-killing chytrid fungus Batrachochytrium dendrobatidis, a prediction we have verified using microscopy and small molecule inhibitors of actin cytoskeletal components. By developing mechanistic definition of distinct modes of crawling motility, and expanding our phylogenetic analysis to many eukaryotes, we are identifying genetic markers and regulatory mechanisms to understand basic principles of this key eukaryotic behavior.