The main feature of podosomes is the F-actin-rich core, which depends on (N)-WASP-triggered activation of the Arp2/3 complex, thus likely consisting of branched actin filaments. The central branched network likely transitions into peripheral actin bundles. The core contains numerous actin regulators such as cortactin or cofilin and most importantly TKS5, a SRC kinase substrate that serves as a scaffold for a variety of podosome components. Oscillatory growth of the podosome core is the basis for podosome protrusion into the surrounding matrix, a prerequisite for podosome functions such as mechanosensing and matrix degradation.



The basal part of the podosome core is surrounded by a discontinuous ring of clusters consisting of adhesive plaque proteins. The ring complex contains proteins like talin-1 and paxillin, which are bound to the intracellular domains of integrins. Additionally, mechanosensitive proteins like vinculin can be recruited to the podosome ring due to a force-dependent exposure of crytpic binding sites. The respective force is generated by growth of the actin core and likely transmitted onto the ring through the lateral cables

The podosome cap is located on the dorsal side of podosomes and stretches over the upper part of the podosome core. The cap consists of actomyosin regulators such as the formin INF2, lymphocyte-specific protein-1 and α-actinin, and probably also regulators of the gradual transition from the branched core to the unbranched and bundled lateral filaments. The precise localization of the individual proteins into the different cap layers and their respective functions within the cap are currently not fully understood.


The podosome cables consist of F-actin bundles which are interconnected by myosinIIA. The cables are divided into two different subsets, the lateral and the connecting cables. The lateral cables connect the top of the podosome core with the ring structure and likely transmit the mechanical forces needed to regulate ring protein recruitment. This force is mainly regulated by the polymerization of actin that drives podosome core growth. The dorsal connecting cables link individual podosomes into superstructures like clusters, rosettes and belts. They show a higher accumulation of myosin IIA than the lateral cables and are thus likely more contractile.

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