Kinetically distinct phases of tau on microtubules regulate kinesin motors and severing enzymes.

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  • Additional Information
    • Source:
      Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Macmillan Magazines Ltd., [1999-
    • Subject Terms:
      Kinesins/*metabolism ; Microtubules/*metabolism ; Neurons/*metabolism ; tau Proteins/*metabolism; Adenosine Triphosphatases/metabolism ; Animals ; Axons/metabolism ; Cells, Cultured ; Katanin/metabolism ; Kinetics ; Neurodegenerative Diseases/metabolism
    • Abstract:
      Tau is an intrinsically disordered protein, which diffuses on microtubules 1 . In neurodegenerative diseases, collectively termed tauopathies, malfunction of tau and its detachment from axonal microtubules are correlated with axonal degeneration 2 . Tau can protect microtubules from microtubule-degrading enzymes such as katanin 3 . However, how tau carries out this regulatory function is still unclear. Here, using in vitro reconstitution, we show that tau molecules on microtubules cooperatively form cohesive islands that are kinetically distinct from tau molecules that individually diffuse on microtubules. Dependent on the tau concentration in solution, the islands reversibly grow or shrink by addition or release of tau molecules at their boundaries. Shielding microtubules from kinesin-1 motors and katanin, the islands exhibit regulatory qualities distinct from a comparably dense layer of diffusible tau. Superprocessive kinesin-8 motors penetrate the islands and cause their disassembly. Our results reveal a microtubule-dependent phase of tau that constitutes an adaptable protective layer on the microtubule surface. We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behaviour and potentially compete with tau in regulating access to the microtubule surface.
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    • Accession Number:
      0 (tau Proteins)
      EC 3.6.1.- (Adenosine Triphosphatases)
      EC 3.6.4.4 (Kinesins)
      EC 5.6.1.1 (Katanin)
    • Publication Date:
      Date Created: 20190905 Date Completed: 20191126 Latest Revision: 20211204
    • Publication Date:
      20231215
    • Accession Number:
      10.1038/s41556-019-0374-6
    • Accession Number:
      31481789