TY  - JOUR
AU  - Cabrales Fontela, Yunior
AU  - Kadavath, Harindranath
AU  - Biernat, Jacek
AU  - Riedel, Dietmar
AU  - Mandelkow, Eckhard
AU  - Zweckstetter, Markus
TI  - Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau.
JO  - Nature Communications
VL  - 8
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-05975
SP  - 1981
PY  - 2017
AB  - 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.
KW  - Actin Cytoskeleton: chemistry
KW  - Actin Cytoskeleton: metabolism
KW  - Actin Depolymerizing Factors: chemistry
KW  - Actin Depolymerizing Factors: metabolism
KW  - Alzheimer Disease: pathology
KW  - Humans
KW  - Hydrophobic and Hydrophilic Interactions
KW  - Microtubule-Associated Proteins
KW  - Microtubules: metabolism
KW  - Molecular Docking Simulation
KW  - Phosphorylation
KW  - Protein Interaction Domains and Motifs
KW  - Serine: metabolism
KW  - tau Proteins: chemistry
KW  - tau Proteins: metabolism
KW  - Actin Depolymerizing Factors (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Serine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29215007
C2  - pmc:PMC5719408
DO  - DOI:10.1038/s41467-017-02230-8
UR  - https://pub.dzne.de/record/139653
ER  -