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Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau

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  • Yunior Cabrales Fontela

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    Universitätsmedizin Göttingen
    Max-Planck-Institut für Biophysikalische Chemie)

  • Harindranath Kadavath

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    Max-Planck-Institut für Biophysikalische Chemie)

  • Jacek Biernat

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE))

  • Dietmar Riedel

    (Max-Planck-Institut für Biophysikalische Chemie)

  • Eckhard Mandelkow

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    CAESAR Research Center)

  • Markus Zweckstetter

    (Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
    Universitätsmedizin Göttingen
    Max-Planck-Institut für Biophysikalische Chemie)

Abstract

Microtubule-associated proteins regulate microtubule dynamics, bundle actin filaments, and cross-link actin filaments with microtubules. In addition, aberrant interaction of the microtubule-associated protein Tau with filamentous actin is connected to synaptic impairment in Alzheimer’s disease. Here we provide insight into the nature of interaction between Tau and actin filaments. We show that Tau uses several short helical segments to bind in a dynamic, multivalent process to the hydrophobic pocket between subdomains 1 and 3 of actin. Although a single Tau helix is sufficient to bind to filamentous actin, at least two, flexibly linked helices are required for actin bundling. In agreement with a structural model of Tau repeat sequences in complex with actin filaments, phosphorylation at serine 262 attenuates binding of Tau to filamentous actin. Taken together the data demonstrate that bundling of filamentous actin and cross-linking of the cellular cytoskeleton depend on the metamorphic and multivalent nature of microtubule-associated proteins.

Suggested Citation

  • Yunior Cabrales Fontela & Harindranath Kadavath & Jacek Biernat & Dietmar Riedel & Eckhard Mandelkow & Markus Zweckstetter, 2017. "Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02230-8
    DOI: 10.1038/s41467-017-02230-8
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