Podosome

Podosomes are conical, actin-rich structures found on the outer surface of the plasma membrane of animal cells. Their size ranges from approximately 0.5 μm to 2.0 μm in diameter. While usually situated on the periphery of the cellular membrane, these unique structures display a polarized pattern of distribution in migrating cells, situating at the front border between the lamellipodium and lamellum. Their primary purpose is connected to cellular motility and invasion; therefore, they serve as both sites of attachment and degradation along the extracellular matrix. Many different specialized cells exhibit these dynamic structures such as invasive cancer cells, osteoclasts, vascular smooth muscle cells, endothelial cells, and certain immune cells like macrophages and dendritic cells. A podosome consists of a core rich in actin surrounded by adhesion and scaffolding proteins. The actin filaments within these structures are highly regulated by many actin nucleators, polymerization activators, actin binding and crosslinking proteins, kinases, small GTPases, and scaffold proteins; therefore, total actin turnover occurs within seconds. To distinguish podosomes from others types of cellular adhesions, the protein Tks5 and WASP (Wiskott–Aldrich syndrome protein) are used as markers alongside actin, cortactin and the Arp2/3 complex to localize and isolate these protrusions because Tks5 and WASP are unique to the podosome when compared with other actin-based cellular structures. In their outward structure, the podosomes demonstrate two distinct features: an actin core and a ring complex. Within the core, coordinators of actin nucleation are found. Specifically, the Arp2/3 complex and WASP when close to the plasma membrane or cortactin when further away comprise this group of proteins. Emanating radially from the dense core of actin are actin filaments reaching to the plasma membrane and between neighboring podosomes. In the ring complex, integrins and integrin-associated proteins serve to connect the cytoskeleton to cell surface integrins forming the outward protrusion.