Podosomes

Podosomes are highly dynamic, actin-rich adhesion structures of monocyte-derived cells, certain transformed fibroblasts and have recently also been discovered in an increasing number of other cell types. Related organelles called invadopodia are formed in cancer cells. Because they are mainly found in motile cells and control the activity of matrix metalloproteases, podosomes are thought to contribute to tissue invasion and matrix remodelling. Regulators of podosome turnover include tyrosine kinases, RhoGTPases, actin regulators and the microtubule system. Importantly, podosomes are physiologically relevant organelles because they can be found inex vivo models of invasive cells.

Podosomes are formed on a physiological substrate. Human peripheral blood monocyte seeded onto confluent layer of human umbilical vein endothelial cells (HUVEC). Podosomes are formed at the leading edge of the migrating cell (cell circumference depicted by white line).Confocal laser scanning micrograph; f-actin (red), vinculin (green), overlay (yellow). (Linder and Aepfelbacher, Trends Cell Biol. 2003)

Podosome model. Lower left panel. Confocal laser scanning micrograph of primary human macrophage, f-actin staining, each bright dot corresponds to a single podosome. Lower right panel: schematic drawing of a podosome, with optical cut perpendicular to the substrate. The plasma membrane is delineated by a black line. Upper left panel: detail of the podosomal ring structure. Integrins mediate ECM binding, while paxillin acts as a scaffold for an intracellular complex containing src.This complex is linked via vinculin, talin and a-actinin to f-actin of the core. Note: only one of several possible states of interaction between the components is depicted. Upper right panel: detail of the podosomal core structure. Actin filaments are nucleated at the membrane via CDC42-activated WASp/N-WASP and Arp2/3 complex. (Linder and Aepfelbacher, Trends Cell Biol., 2003).

Subpopulations of podosomes.
Image from confocal time lapse movie, podosomes are artificially color-coded according to their behavior. Note that dynamic podosomes concentrate at the cell periphery, where larger precursor clusters mostly undergo fission, while smaller podosomes mostly dissolve. By contrast, small, static podosomes cluster at the center of the substrate-attached cell side. Size bar: 10 µm. (Kopp et al., Mol. Biol. Cell, 2006).