Tau protein is a protein of significant interest, as its hyperphosphorylated pathological form has been implicated in many neurological diseases, including Alzheimer's disease. While it was initially characterized as a microtubule-stabilizing protein, more recent studies suggest it can also alter microtubule nucleation and aggregation. A previous and still growing area of research for tau relates to its ability to form condensates with RNA, and now work by Park et. al. examines tau’s interaction with DNA and how it impacts microtubules and their downstream functions. Preliminary studies using biochemical and single-molecule imaging showed that DNA and tau can form an electrostatic interaction that led to DNA compaction through interaction with multiple tau proteins, which ultimately led to tau-DNA co-condensates. The group then developed a microtubule capture assay, where their surface-bound tau-DNA co-condensates were exposed to a mixture of tau and tubulin. The tau-DNA co-condensates effectively captured microtubules. Effective capturing of microtubules diminished significantly when co-condensation of tau and DNA did not occur. The group also investigated how tau phosphorylation altered its binding to DNA, and found that while phosphorylated tau can reduce its affinity for DNA and microtubules, it still interacts with wild-type tau and DNA co-condensates. They then examined this phenomenon in cell culture via microscopy-based approaches and observed strong tau clustering with both microtubules and centromeres. Ultimately, they propose that these tau clusters may be important for registration of mitotic spindles to chromosomes before the kinetochore-mediated attachment, implicating a role for it in mitosis. Cytoskeleton Inc.’s purified unlabeled tubulin (Cat. # T240) and fluorescently labeled tubulin (Cat.TL590M) were foundational tools for studying how these tau-DNA co-condensates interacted with microtubules in vitro.
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Product Used in Citation:
Tubulin protein (>99% pure): porcine brain (Cat # T240)
Tubulin protein (rhodamine): porcine brain (Cat # TL590M)
