{
  "abstract": "In cells, myosin Va and kinesin-1 motors navigate their shared vesicular cargos through numerous actin-microtubule (MT) intersections. How cargos exit these intersections to ensure precise destination delivery remains unclear. We hypothesized that the myosin Va adapter melanophilin -- a phosphorylated protein that links myosin Va to melanosomes but can also bind actin and MTs -- acts as a phosphorylation-dependent switch to bias the tug-of-war between cargo-bound myosin Va and kinesin-1 at actin-MT intersections. We modeled melanosome transport in vitro using 350-nm liposomes with ~5 each of surface-bound constitutively active myosin Va and kinesin-1, and ~5 full-length melanophilin with varying phosphorylation levels. Regardless of the track the liposome entered the actin-MT intersection on, phosphorylated melanophilin biased liposomes to exit on actin, whereas dephosphorylated melanophilin biased liposomes to exit on MTs. Consistent with this, phosphorylated melanophilin preferentially bound actin 2-fold over MTs, and slowed myosin Va liposome transport on actin by ~40%, effectively acting as an anchor. Conversely, dephosphorylated melanophilin preferentially bound (2-fold) MTs over actin, and increased kinesin-1 liposome transport distance on MTs by acting as a tether. Therefore, melanophilin, depending on its phosphorylation state, biases track selection by kinesin-1/myosin Va transported cargos in actin-MT intersections that exist in complex cellular cytoskeletal networks.",
  "abstract_shown": true,
  "affiliations": [
    "University of Vermont Larner College of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "B. M. Bensel"
    },
    {
      "name": "P. M. Fagnant"
    },
    {
      "name": "J. E. Macfarlane"
    },
    {
      "name": "M. J. Previs"
    },
    {
      "name": "K. M. Trybus"
    },
    {
      "affs": [
        0
      ],
      "name": "D. M. Warshaw"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a4becabbnd5z7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748553",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748553v1.full",
  "id": "a4becabbnd5z7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748553v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "openalex",
      "1307|Microtubule and mitosis dynamics"
    ]
  ],
  "openalex": "W7207758759",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748553v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a4becabbnd5z7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:37Z",
      "native_id": "10.64898/2026.09.01.748553",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748553v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Melanophilin, a Myosin Va Adapter Protein, Biases Track Selection of Myosin Va-and Kinesin-1-Transported Liposomes at Actin-Microtubule Intersections In Vitro",
  "title_text": "Melanophilin, a Myosin Va Adapter Protein, Biases Track Selection of Myosin Va-and Kinesin-1-Transported Liposomes at Actin-Microtubule Intersections In Vitro",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:07Z",
  "url": "https://research.draconitic.com/paper/a4becabbnd5z7",
  "venue": "bioRxiv",
  "versions": []
}