{
  "abstract": "Lipid transfer proteins (LTPs) mediate non-vesicular lipid transport at membrane contact sites, yet how transient membrane tethering contributes to lipid transfer remains poorly understood. Here, we use the single-domain yeast phosphatidylserine transporter Osh6, a member of the oxysterol-binding protein-related protein family, to investigate tethering-dependent lipid transport. We show that Osh6 can access two transport modes depending on membrane composition: conventional shuttling between membranes and a tethering-dependent mode in which the opposing membrane facilitates cargo extraction from the donor membrane. Combining lipid transport and membrane-tethering measurements with kinetic analysis, lipid partitioning, and in vivo complementation, we provide evidence for a transient membrane-bridged intermediate during lipid transfer. Productive phosphatidylinositol 4-phosphate (PI4P) extraction destabilizes this bridged state, allowing cargo-loaded Osh6 to disengage and continue the transport cycle. We term this mechanism kiss-and-ride, in which transient membrane contact facilitates cargo extraction (\"kiss\") before the cargo-loaded protein disengages (\"ride\"). Consistent with this model, PI4P transport is preserved in a lidless Osh6 mutant with impaired membrane dissociation, whereas phosphatidylserine transport is strongly reduced, revealing distinct mechanistic requirements for the two cargoes. Together, our findings reveal a tethering-dependent transport mode in a cup-like LTP and suggest that membrane contact sites can actively shape the mechanism of lipid transport rather than merely bringing donor and acceptor membranes into proximity.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Organic Chemistry and Biochemistry of the CAS, Prague"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "A. Ballekov"
    },
    {
      "name": "A. Eisenreichov"
    },
    {
      "name": "R. Holic"
    },
    {
      "name": "P. Griac"
    },
    {
      "name": "E. Boura"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Humpolickova"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/21h2nv020hg3q.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.29.755298",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755298v1.full",
  "id": "21h2nv020hg3q",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755298v1",
  "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",
      "1307|Cellular transport and secretion"
    ]
  ],
  "openalex": "W7219795163",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755298v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/21h2nv020hg3q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:57Z",
      "native_id": "10.64898/2026.09.29.755298",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755298v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "A Kiss-and-Ride Mechanism for Lipid Exchange at Membrane Contact Sites",
  "title_text": "A Kiss-and-Ride Mechanism for Lipid Exchange at Membrane Contact Sites",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:57Z",
  "url": "https://research.draconitic.com/paper/21h2nv020hg3q",
  "venue": "bioRxiv",
  "versions": []
}