The dynamics of podosomes, extracellular matrix-associated proteins regulate the cytoskeletal remodeling, mechanosensing, migration in Tau.

The formation of filopodia and podosome-like structures as a part of the Alzheimer's disease pathology has been examined over the recent past. Podosomes are structures rich in F-actin, which are involved in adhesion and mechanosensing. To assist the podosomes in its roles, it has an advanced and dynamic structure, comprised of actin filaments as a part of its core, the ring region composed of integrin and integrin-actin linkers and the cap composed of tropomyosin 4. The podosomes organize from clusters to rings to belts. Various components are involved in the formation of podosomes, including phosphatidylinositol, Src kinases, PI3 kinase, the adaptor TKS5, integrins, cortactin, paxillin, Iba1, Sk3, PAM, EB1, CDC42, WASP and Arp2/3. Podosomes play a role in cell adhesion by attaching cells to the ECM, while also contributing to the latter's degradation. Many studies have also shown that podosomes and invadosomes are involved in pathogen clearance. Various factors responsible for the formation of podosomes have also been linked to the Alzheimer's disease, including TKS5 and ADAM12 which have been liked to Amyloid-β. TKS5 and Arp2 are involved in the interactions between the P2Y12 receptor and Tau, which lead to the formation of podosomes. It is suggested that these podosomes are involved in the microglial migratory process.