송채연 (University of California, Santa Barbara (현 AMOREPACIFIC R&D Center))

한빛사논문

조회336

University of California, Santa Barbara (현 AMOREPACIFIC R&D Center)

CV File 240 kb

Nat. Commun., Mar 15 2024, 15 (1) 2362 | https://doi.org/10.1038/s41467-024-46438-x Complexes of tubulin oligomers and tau form a viscoelastic intervening network cross-bridging microtubules into bundles

Phillip A. Kohl ^1,12, Chaeyeon Song ^2,3,4,5,8,12, Bretton J. Fletcher ^2,3,4,5,12, Rebecca L. Best ^4,6,9, Christine Tchounwou ^2,3,4,5, Ximena Garcia Arceo ^5,10, Peter J. Chung ^2,3,4,5,11, Herbert P. Miller ⁴, Leslie Wilson ^4,6, Myung Chul Choi ⁷, Youli Li ^1,*, Stuart C. Feinstein^4,6 & Cyrus R. Safinya ^2,3,4,5,*

¹Materials Research Laboratory, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
²Materials Department, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
³Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁴Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
⁵Department of Physics, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁶Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁷Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Daejeon 34141, Korea.
⁸Present address: Amorepacific R&I Center, Yongin 17074, Republic of Korea.
⁹Present address: Serimmune Inc., 150 Castilian Dr., Goleta, CA 93117, USA.
¹⁰Present address: Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA 93106, USA.
¹¹Present address: Department of Physics and Astronomy, University of Southern California, Los Angeles, CA 90089, USA.
¹²These authors contributed equally: Phillip A. Kohl, Chaeyeon Song, Bretton J. Fletcher.

^*Corresponding authors: correspondence to Youli Li or Cyrus R. Safinya

Abstract

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 Mg²⁺ or Ca²⁺ 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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-19)
연구진국내+국외 연구진
분야 생명과학 > 구조생물 및 생물물리학

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