{
  "abstract": "Tau is a microtubule (MT)-associated protein essential for neuronal cytoskeletal organization and intracellular transport, yet how tau physically regulates motor proteins remains elusive. Here, we integrate single-molecule imaging, cryo-electron microscopy, and molecular dynamics (MD) simulations to investigate the molecular mechanisms underlying tau-mediated inhibition of kinesin-1 and cytoplasmic dynein motility. We show that tau suppresses MT landing and triggers frequent pausing and premature detachment when motors encounter tau-enriched patches. Unexpectedly, tau impairs each motor using different mechanisms. Tau and kinesin-1 compete for the same surface on tubulin, precluding simultaneous binding to the same MT site. On the other hand, while dynein and tau can co-occupy the same tubulin, tau inhibits the transition of dynein into its high-affinity MT-binding state. Thus, tau can act as a physical or a conformational roadblock in a concentration-dependent manner, exerting distinct structural constraints on kinesin and dynein transport. These findings establish a structural framework for tau-mediated regulation of axonal transport.",
  "abstract_shown": true,
  "affiliations": [
    "UC Berkeley"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Y. He"
    },
    {
      "name": "J. Peukes"
    },
    {
      "name": "M. Golcuk"
    },
    {
      "name": "A. Y. Jack"
    },
    {
      "name": "L. S. Ferro"
    },
    {
      "name": "R. Tan"
    },
    {
      "name": "M. Gur"
    },
    {
      "affs": [
        0
      ],
      "name": "E. Nogales"
    },
    {
      "name": "A. Yildiz"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8nwx56m1z9407.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.02.763819",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763819v1.full",
  "id": "8nwx56m1z9407",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763819v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763819v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8nwx56m1z9407.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T00:21:42Z",
      "native_id": "10.64898/2026.11.02.763819",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763819v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "The Molecular Interplay of Tau and Motor Proteins on Microtubules",
  "title_text": "The Molecular Interplay of Tau and Motor Proteins on Microtubules",
  "type": "preprint",
  "updated_at": "2026-11-06T00:21:27Z",
  "url": "https://research.draconitic.com/paper/8nwx56m1z9407",
  "venue": "bioRxiv",
  "versions": []
}