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Fig. 1 | Cell & Bioscience

Fig. 1

From: Microglia degrade Tau oligomers deposit via purinergic P2Y12-associated podosome and filopodia formation and induce chemotaxis

Fig. 1

Tau oligomers induce podosome and filopodia formation, orchestrated with Arp2. A Extracellular Tau oligomers-induced podosome accumulation more in microglial lamellipodia, than Tau monomers as observed by immunofluorescence (IF) assay. The microglial podosome was found to be colocalized with actin-nucleator protein Arp2 for rapid actin polymerization in response to Tau oligomers similar to ADP exposure in migratory microglia (scale bar 10 μm). B A simplistic illustration of podosome where actin cross-linking is mediated by actin nuclear Arp2/3 complex. The actin cores are surrounded by the vinculin ring and adhesion protein receptors. The attachment of actin core fibers with membrane receptors is driven by adaptor protein TKS5. C The quantification of microscopic images showed that the exposure of Tau oligomers has significantly induced the podosome+ microglia by 70% as compared to the monomer-exposed group (50%). (No. of experiment = 3) (n = 13). D Moreover, podosome-associated area has increased almost twice in Tau-exposed microglial cells as compared to cell control. (No. of experiment = 3) (n = 40). E Tau oligomers have increased the number of filopodia three times more compared to untreated control microglia. While, the Tau monomer and ADP exposure have induced the filopodia numbers twice than the control population, as seen by microscopic image quantification. (No. of experiment = 3) (n = 50). F Similar to podosome, Tau oligomers facilitated the localization of Arp2 in filopodia and branched uropod in microglia, for actin polymerization during migration (scale bar 10 μm). G The Arp2 level was reduced from microglial uropod upon Tau oligomers exposure, relating rapid actin dynamics towards frontal lamellipodia. (No. of experiment = 3) (n = 50). H, I. The Arp2 expression level remained unaltered in various Tau and ADP exposure by Western blot analysis and relative fold change calculation in N9 microglia. (n = 3). J The extracellular Tau oligomers have the potential to induce the accumulation of podosome and filopodia by localizing Arp2 at lamellipodia of microglia, which plays an essential role in migration and mechanosensing

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