Complexes of tubulin oligomers and tau form a viscoelastic intervening network cross-bridging microtubules into bundles.

Autor: Kohl PA; Materials Research Laboratory, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA., Song C; Materials Department, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Amorepacific R&I Center, Yongin, 17074, Republic of Korea., Fletcher BJ; Materials Department, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA., Best RL; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Serimmune Inc., 150 Castilian Dr., Goleta, CA, 93117, USA., Tchounwou C; Materials Department, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA., Garcia Arceo X; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, 93106, USA., Chung PJ; Materials Department, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.; Department of Physics and Astronomy, University of Southern California, Los Angeles, CA, 90089, USA., Miller HP; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA., Wilson L; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA., Choi MC; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Daejeon, 34141, Korea., Li Y; Materials Research Laboratory, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. youli@mrl.ucsb.edu., Feinstein SC; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA., Safinya CR; Materials Department, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. cyrussafinya@ucsb.edu.; Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. cyrussafinya@ucsb.edu.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA. cyrussafinya@ucsb.edu.; Department of Physics, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA. cyrussafinya@ucsb.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 15; Vol. 15 (1), pp. 2362. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1038/s41467-024-46438-x
Abstrakt: The axon-initial-segment (AIS) of mature neurons contains microtubule (MT) fascicles (linear bundles) implicated as retrograde diffusion barriers in the retention of MT-associated protein (MAP) tau inside axons. Tau dysfunction and leakage outside of the axon is associated with neurodegeneration. We report on the structure of steady-state MT bundles in varying concentrations of Mg 2+ or Ca 2+ divalent cations in mixtures containing αβ-tubulin, full-length tau, and GTP at 37 °C in a physiological buffer. A concentration-time kinetic phase diagram generated by synchrotron SAXS reveals a wide-spacing MT bundle phase (B ws ), a transient intermediate MT bundle phase (B int ), and a tubulin ring phase. SAXS with TEM of plastic-embedded samples provides evidence of a viscoelastic intervening network (IN) of complexes of tubulin oligomers and tau stabilizing MT bundles. In this model, αβ-tubulin oligomers in the IN are crosslinked by tau's MT binding repeats, which also link αβ-tubulin oligomers to αβ-tubulin within the MT lattice. The model challenges whether the cross-bridging of MTs is attributed entirely to MAPs. Tubulin-tau complexes in the IN or bound to isolated MTs are potential sites for enzymatic modification of tau, promoting nucleation and growth of tau fibrils in tauopathies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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