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A PCP (arrowhead) turns into four podosomes (arrows) during migration.

Macrophages crawl across a substrate using podosomes, focal complex-like adhesions that form and disappear rapidly at the cell's leading edge. Beginning on page 697, Evans et al. provide a high-resolution view of the dynamic turnover of these structures, revealing some surprising behavior and suggesting a novel mechanism of cell migration.

Using fluorescently labeled podosome components and quantitative 4-D microscopy, the authors show that the majority of leading edge podosomes either assemble from older podosomes or form through the dramatic fragmentation of a large podosome cluster precursor (PCP). In the first pathway, simple podosomes undergo both fission and fusion events. This often produces a sort of forward stepping movement, when a trailing podosome fuses with one closer to the leading edge. The other pathway begins with a podosome that grows to several times normal size to form a PCP. The PCP then fragments rapidly into a cluster of four to six individual podosomes.

In contrast to focal adhesions, which stick to a substrate and allow a cell to pull itself forward, podosomes appear to step forward more or less continuously. This dynamic crawl may allow macrophages to adapt quickly while moving through complex tissues. ▪