Journal Article

DZNE-2020-05975

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau.

Cabrales Fontela, Y. (First author)DZNE* ; Kadavath, H.DZNE* ; Biernat, J.DZNE* ; Riedel, D. ; Mandelkow, E.DZNE* ; Zweckstetter, M. (Last author)DZNE*

2017
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-017-02230-8

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.

Keyword(s): Actin Cytoskeleton: chemistry (MeSH) ; Actin Cytoskeleton: metabolism (MeSH) ; Actin Depolymerizing Factors: chemistry (MeSH) ; Actin Depolymerizing Factors: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Humans (MeSH) ; Hydrophobic and Hydrophilic Interactions (MeSH) ; Microtubule-Associated Proteins (MeSH) ; Microtubules: metabolism (MeSH) ; Molecular Docking Simulation (MeSH) ; Phosphorylation (MeSH) ; Protein Interaction Domains and Motifs (MeSH) ; Serine: metabolism (MeSH) ; tau Proteins: chemistry (MeSH) ; tau Proteins: metabolism (MeSH) ; Actin Depolymerizing Factors ; Microtubule-Associated Proteins ; tau Proteins ; Serine

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Contributing Institute(s):

1. Translational Structural Biology (AG Zweckstetter)
2. Structural Principles of Neurodegeneration (AG Mandelkow 1)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

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Database coverage:
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