Podosomes are adhesive structures and so unsurprisingly they contain many of the same proteins found in focal adhesions (FAs), such as talin,vinculin, paxillin and Src family proteins [3]. An exception to this generality is the protein Tks5 (tyrosine kinase substrate with five SH3 domains), which is found in podosomes and invadopodia, but not in FAs or any other actin-based structures. WASP (Wiskott Aldrich Syndrome protein) shows even greater specificity, being unique to podosomes. Tks5 and WASP can therefore be used as markers alongside actin, cortactin and the Arp2/3 complex to identify these unique protrusions [4].

The ring complex comprises integrins and integrin-associated proteins, such as paxillin [10] 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 [11]. These findings were obtained by applying novel super-resolution analysis (Bayesian Blinking and Bleaching (3B) analysis) to data acquired by standard widefield microscopy of cells expressing fluorescently tagged proteins that localize to the podosome ring complex. The increased resolution of the images also suggested that different proteins within the ring complex have distinct localizations, with vinculin appearing more peripherally to talin [11].

In general, the podosome structure is no greater than approximately 0.5 μみゅーm in width and 1 μみゅーm in depth [10]. The lifetime of this structure is far shorter than that of focal adhesions, lasting only a few minutes [12].

Further evidence for the role of podosomes in cell migration, comes from the immune cells of Wiskott-Aldrich Syndrome patients. These patients lack full length WASP(Wiskott-Aldrich Syndrome protein), which is known to localize to podosomes and is required for their formation. Both the dendritic cells [15] and macrophages [16] of these patients lack podosomes and as a consequence show migratory defects [15, 16]. There is currently speculation that podosomes may also be important in the migration of neural crest cells, due to the neural crest-associated defects seen in Frank-ter Haar patients, who are mutant for the podosome- and invadopodia-specific protein Tks5 [4].

In addition to the roles ascribed above, the idea of podosomes having mechanosensory potential has also been posited [9, 17, 18, 19]. The initiation of podosome formation has been shown to be dependent on the underlying matrix, both in terms of its nature (which ligands are present) and its geometry (whether the ligands are uniformly distributed or arranged in subcellular-sized islands). Cells use different integrin receptors to detect the mechanical constraints of their environment and to decide accordingly whether a podosome should be initiated or not [17]. Following initiation, substrate stiffness continues to play a role in the lifespan of the podosome, with increased stiffness resulting in increased longevity and decreased distance between individual podosomes [18].

Once formed, the podosome itself is hypothesized to exhibit mechanosensory characteristics, transmitting mechanical forces both from the inside-out and outside-in [9]. This was suggested following a series of experiments examining the actomyosin network of the podosome. Myosin II was detected in and around the adhesive ring of the podosome. Changes in the size and shape of the adhesive ring were shown to result in changes in tractional forces against the underlying substrate (inside-out force transmission), in a myosin-dependent manner. Moreover, increasing substrate stiffness, increased the strength of these tractional forces (outside-in force transmission).

The structural changes that occur during osteoclast maturation involve the accumulation of F-actin, vinculin, paxillin and αあるふぁ-actinin specifically within podosomes of the forming ring structure [21]. Signaling changes also occur within these podosomes, such as reduced levels of Src-mediated phosphorylation [21]. The podosome protein, cortactin, specifically shows reduced levels of tyrosine phosphorylation, which is suggested to enhance its actin-nucleating activity [22].

Upon bone resorption, the podosome belt is dismantled, leaving behind a ring-like F-actin mesh encompassing the 'sealing zone' [23]. The sealing zone forms the attachment of the osteoclast to the underlying bone and is essential to the process of bone resorption. The inhibition of bone resorption by drug treatment results in loss of the characteristic podosome belt around the cell periphery. Podosomes are therefore believed to play an important role in formation of the sealing zone and bone resorption[23].