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. ▪