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Cited by 2Cellular transport and secretionMicrotubule and mitosis dynamicsFungal and yeast genetics research

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Cargo adaptors use a handhold mechanism to engage with myosin V for organelle transport

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Hahn, Hye Jee, Pashkova, Natalya, Cianfrocco, Michael A., Weisman, Lois S.·2025·Journal of Cell Biology
DOI 10.1083/jcb.202408006PMC PMC11974856

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Abstract

Myo2, a class V myosin motor, is essential for organelle transport in budding yeast. Its association with cargo is regulated by adaptor proteins that mediate both attachment and release. Vac17, a vacuole-specific adaptor, links Myo2 to the vacuole membrane protein Vac8 and plays a key role in assembling and disassembling the Myo2–Vac17–Vac8 complex during vacuole inheritance. Using genetics, cryo-EM, and structure prediction, we find that Vac17 interacts with Myo2 at two distinct sites rather than a single interface. Similarly, the peroxisome adaptor Inp2 engages two separate regions of Myo2, one of which overlaps with a Vac17-binding site. These findings support a “handhold” model, in which cargo adaptors occupy multiple surfaces on the Myo2 tail, which likely enhances motor–cargo associations as well as provide additional regulatory control over motor recruitment.

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Metadata

Authors
Hahn, H. J., Pashkova, N., Cianfrocco, M. A., & Weisman, L. S.
Affiliations
  • University of Michigan (US)
  • University of Iowa (US)
Corresponding author
  • Cianfrocco, Michael A.
  • Weisman, Lois S.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2025-05-16
Volume
224
Issue
7
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.202408006
PMC
PMC11974856
OpenAlex
W4410439098
Cited by
2
References
1
Citations by year
2026: 1 · 2025: 1
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
rupress.org/pages/terms102024 (vor)
Locations
  • The Journal of Cell Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • PubMed Central (submittedVersion)
Funders
  • University of Michigan Cryo-EM Facility
  • University of Michigan Biosciences Initiative
  • National Institutes of Health (R01-GM062261, S10OD020011)
  • University of Michigan Rackham Predoctoral Fellowship
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Myo2, myosin V, cargo adaptors, organelle transport, vacuole inheritance, Saccharomyces cerevisiae

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