Fig. 4

Extracellular Tau facilitates P2Y12 localization in filopodia and uropod, which degrades Tau deposits. A P2Y12 was colocalized with F-actin in filopodia and branched uropod of migratory microglia. Extracellular Tau oligomers exposure induced the localization of P2Y12 more in microglial filopodia and uropod as compared to monomer-treated cells. (Scale bar 10 μm) B The P2Y12⁺ filopodia⁺ microglia has significantly increased up to 80% upon Tau oligomers exposure than monomer exposure at 50%. (No. of experiment = 3) (n = 22). C P2Y12 intensity has increased in uropod by Tau oligomers and ADP exposure in migratory microglia (No. of experiment = 3) (n = 50). D The coverslips were coated with Tau monomer and oligomers to mimic the scenario of Tau depositions. The N9 microglia were seeded onto the coated coverslip to determine the potency of Tau plaques degradation. Microglia degraded Tau monomeric deposits by 8 h and Tau oligomers deposits by 24 h after seeding, through the formation of the F-actin-rich P2Y12⁺ podosome. It was evident that the degradation of Tau monomers was faster than oligomeric deposits (scale bar 10 μm). E The percentage of microglia, which degraded Tau monomer- deposits, was 38%, while 30% of microglia degraded Tau oligomers deposits. (No. of experiment = 3) (n = 40). F The P2Y12-associated podosome in microglia degraded Tau monomer deposits more than Tau oligomers-deposits. (No. of experiment = 3) (n = 30). G Microglia was also found to degrade Tau deposits through filopodia formation, which was orchestrated with P2Y12 (scale bar 10 μm). It was evident for the first time that P2Y12⁺ filopodia could degrade Tau monomer and oligomers deposits, which connects the signaling of chemotaxis and matrix degradation. H Microglia degraded the Tau deposits more in the case of the Tau monomer than the Tau oligomers deposits, through the formation of P2Y12⁺ filopodia. (No. of experiment = 3) (n = 30). I Extracellular Tau oligomers have induced the P2Y12-driven chemotaxis, which leads to the substratum adhesion and Tau deposit degradation through the formation of podosome and filopodia in migratory microglia