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Cited by 5Microtubule and mitosis dynamicsAlzheimer's disease research and treatmentsCancer Treatment and Pharmacology

Tau and MAP6 establish labile and stable domains on microtubules

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Kirimtay, Koray, Huang, Wenqiang, Sun, Xiaohuan, Qiang, Liang, Wang, Dong V., Sprouse, Fern C., Craig, Erin M., Baas, Peter W.·2025·iScience
DOI 10.1016/j.isci.2025.111785PMC PMC11879653
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Abstract

We previously documented that individual microtubules in the axons of cultured juvenile rodent neurons consist of a labile domain and a stable domain and that experimental depletion of tau results in selective shortening and partial stabilization of the labile domain. After first confirming these findings in adult axons, we sought to understand the mechanism that accounts for the formation and maintenance of these microtubule domains. We found that fluorescent tau and MAP6 ectopically expressed in RFL-6 fibroblasts predominantly segregate on different microtubules or different domains on the same microtubule, with the tau-rich ones becoming more labile than in control cells and the MAP6-rich ones being more stable than in control cells. These and other experimental findings, which we studied further using computational modeling with tunable parameters, indicate that these two MAPs do not merely bind to pre-existing stable and labile domains but actually create stable and labile domains on microtubules.

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  • Such regional variation is consistent with previous studies and suggests that lattice conformation can be locally influenced by lattice-binding microtubule-associated proteins, post-translational modifications, mechanical stress, or repair processes.

    “Such regional variation is consistent with previous studies58and suggest that lattice conformation can be locally influenced by lattice-binding microtuble-associated proteins (MAPs)59–61, post-translational modifications, mechanical stress50,51, or repair processes62–66.”

    From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [60]

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Cited by

Sorted by citations

Authors
Kirimtay, K., Huang, W., Sun, X., Qiang, L., Wang, D. V., Sprouse, F. C., Craig, E. M., & Baas, P. W.
Affiliations
  • Drexel University (US)
  • Central Washington University (US)
Corresponding author
Baas, Peter W.
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2025-03
Volume
28
Issue
3
Pages
111785
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2025.111785
PMC
PMC11879653
OpenAlex
W4406942850
Cited by
5
References
5
Citations by year
2026: 5
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (R01NS115977, 1915477)
  • US Office of Congressionally Directed Medical Research Programs (W81XWH2110189)
  • Alzheimer's Association (24AARG-D-1191264)
  • Christopher and Dana Reeve Foundation
  • U.S. Department of Defense
  • National Institute on Aging (R21AG068597)
  • National Institute of Neurological Disorders and Stroke (R01NS28785)
  • National Institutes of Health
  • Ionis Pharmaceuticals
  • Drexel University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
tau protein, MAP6, microtubule stability, microtubule dynamics, microtubule stabilization, axons, microtubule-associated proteins

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