The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility

Zhao, X.-T.; Diep, D. T. V.; Percifull, L.; Fausten, R. M.; Hugenroth, M.; Höhne, P.; Esch, B. M.; Collado, J.; Keller, J.; Wilmes, S.; Wälte, M.; Kümmel, D.; Schuberth, C.; Fernandez-Busnadiego, R.; Fröhlich, F.; Wedlich-Söldner, R.; Bohnert, M.

doi:10.1101/2025.02.21.639583

bioRxiv · 10.1101/2025.02.21.639583

The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility

Zhao, X.-T.·Diep, D. T. V.·Percifull, L.·Fausten, R. M.·Hugenroth, M.·Höhne, P.·Esch, B. M.·Collado, J.·Keller, J.·Wilmes, S.·Wälte, M.·Kümmel, D.·Schuberth, C.·Fernandez-Busnadiego, R.·Fröhlich, F.·Wedlich-Söldner, R.·Bohnert, M.

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Abstract

Organelle motility enables strategic cellular reorganizations. In yeast, this process depends on the actin cytoskeleton, type V myosin motor proteins, and organelle-specific myosin adaptor proteins. While the myosin adaptors for most organelles are known, the coupling of myosin to lipid droplets (LDs), the cellular lipid storage organelles, remained enigmatic. Using genome-wide screening, we identified Ldm1 (Lipid Droplet Motility 1/Yer085c) as a myosin adaptor. Ldm1 binds to the globular tail domain of the myosin Myo2 and to the LD surface protein Ldo16 to enable actin-dependent LD motility. Ldo16 has additional roles in LD contact sites to the vacuole and the ER, suggesting a coordination of LD motility and organelle tethering. Ldm1 has a second role in mitochondrial transport and elevated Ldm1 levels rescue defects of the mitochondrial Myo2-adaptors Mmr1/Ypt11. Our work identifies the molecular machinery for LD motility and contributes to a comprehensive understanding of acto-myosin-based cellular reorganization.

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Zhao, X.-T., Diep, D. T. V., Percifull, L., Fausten, R. M., Hugenroth, M., Höhne, P., Esch, B. M., Collado, J., Keller, J., Wilmes, S., Wälte, M., Kümmel, D., Schuberth, C., Fernandez-Busnadiego, R., Fröhlich, F., Wedlich-Söldner, R., Bohnert, M.. 2025-02-23. The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility. https://doi.org/10.1101/2025.02.21.639583

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