Tau and MAP6 establish labile and stable domains on microtubules.

1. iScience. 2025 Jan 29;28(3):111785. doi: 10.1016/j.isci.2025.111785. eCollection 2025 Mar 21. Tau and MAP6 establish labile and stable domains on microtubules. Kirimtay K(1), Huang W(1), Sun X(1), Qiang L(1), Wang DV(1), Sprouse CT(2), Craig EM(2), Baas PW(1). Author information: (1)Department Neurobiology and Anatomy, Drexel University, 2900 Queen Lane, Philadelphia, PA 19129, USA. (2)Department Physics, Central Washington University, Ellensburg, WA 98926, USA. 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. © 2025 The Author(s). DOI: 10.1016/j.isci.2025.111785 PMCID: PMC11879653 PMID: 40040809 Conflict of interest statement: The authors declare no competing interests.