Podosomes are actin-rich, adhesive structures that are present at the ventral surface of cells of the monocytic myeloid lineage, stimulated endothelial cells, and cultured Src-transformed cancer cells. These structures are not limited to the cell periphery, but do exhibit a polarized distribution pattern in migrating cells, localizing to the front at the border between the lamellipodium and the lamellum. Structurally, the podosome is characterized by two main features – an actin core and a ring complex. The actin core contains several coordinators of actin nucleation, namely the Arp2/3 complex and WASP proximal to the plasma membrane and cortactin or HS-1 (hematopoietic lineage cell-specific protein 1) more distally. Further to the dense actin network forming the core, actin filaments emanate radially from the actin core to the plasma membrane and between individual podosomes. The ring complex comprises integrins and integrin-associated proteins, such as paxillin and serves to connect cell surface integrins with the cytoskeleton. Originally thought to be a round structure, recent advances in bioimaging have shown the ring complex to have a polygonal shape. In general, the podosome structure is no greater than approximately 0.5 μm in width and 1 μm in depth. The lifetime of this structure is far shorter than that of focal adhesions, lasting only a few minutes.
Focal adhesions are integrin-containing, multi-protein structures that form mechanical links between intracellular actin bundles and the extracellular matrix or substrate in many cell types. Focal adhesions contain high levels of vinculin, talin, paxillin, zyxin, α-actinin, VASP, FAK, phosphotyrosine proteins, integrin αVβ3 and actopaxin. They are commonly found at the ventral surface of cells in 2-dimensional tissue culture and can be envisioned as the feet of the cell. Focal adhesions act as molecular clutches that provide grip to the substrate for the lamellipodium to protrude forward during motility. Focal adhesion formation is initiated by receptor-matrix binding along the cell periphery at the leading edge. These early complexes, referred to as “nascent adhesions”, initially attach to actin filaments via adaptor proteins such as talin. Growing adhesions increase the traction on the substrate, slow down the actin retrograde flow, aid force transduction along the attached actin bundles and in turn, reinforce the linkage to actin by recruitment of additional scaffolding and signaling components. Further, traction forces exerted by actomyosin contractions and resulting signal transduction events such as phosphorylation of components by focal adhesion kinase promote adhesion maturation and the formation of stress fibers in the lamellum.
Both focal adhesions and podosomes are intimately involved in cell motility, with podosomes specifically implicated in cell invasion. Invasiveness is achieved through the secretion of matrix metalloproteinases (MMPs) from the core of podosomes, which degrade the extracellular matrix (ECM).