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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7 July 2025
Article|
May 16 2025
Cargo adaptors use a handhold mechanism to engage with myosin V for organelle transport
Hye Jee Hahn
,
Hye Jee Hahn
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Department of Cell and Developmental Biology,
University of Michigan
, Ann Arbor, MI, USA
2
Life Sciences Institute, University of Michigan
, Ann Arbor, MI, USA
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Natalya Pashkova
,
Natalya Pashkova
(Investigation)
4Department of Molecular Physiology and Biophysics,
Carver College of Medicine, University of Iowa
, Iowa City, IA, USA
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Michael A. Cianfrocco
,
(Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
2
Life Sciences Institute, University of Michigan
, Ann Arbor, MI, USA
3Department of Biological Chemistry,
University of Michigan
, Ann Arbor, MI, USA
Michael A. Cianfrocco: [email protected]
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Lois S. Weisman
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1Department of Cell and Developmental Biology,
University of Michigan
, Ann Arbor, MI, USA
2
Life Sciences Institute, University of Michigan
, Ann Arbor, MI, USA
Correspondence to Lois S. Weisman: [email protected]
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Hye Jee Hahn
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Department of Cell and Developmental Biology,
University of Michigan
, Ann Arbor, MI, USA
2
Life Sciences Institute, University of Michigan
, Ann Arbor, MI, USA
Natalya Pashkova
Investigation
4Department of Molecular Physiology and Biophysics,
Carver College of Medicine, University of Iowa
, Iowa City, IA, USA
Michael A. Cianfrocco
Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
2
Life Sciences Institute, University of Michigan
, Ann Arbor, MI, USA
3Department of Biological Chemistry,
University of Michigan
, Ann Arbor, MI, USA
Lois S. Weisman
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing
1Department of Cell and Developmental Biology,
University of Michigan
, Ann Arbor, MI, USA
2
Life Sciences Institute, University of Michigan
, Ann Arbor, MI, USA
Correspondence to Lois S. Weisman: [email protected]
Michael A. Cianfrocco: [email protected]
Disclosures: The authors declare no competing interests exist.
Received:
August 02 2024
Revision Received:
February 28 2025
Accepted:
April 30 2025
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
University of Michigan Cryo-EM Facility
Funder(s):
University of Michigan Biosciences Initiative
Funder(s):
National Institutes of Health
- Award Id(s): R01-GM062261,S10OD020011
Funder(s):
University of Michigan Rackham Predoctoral Fellowship
© 2025 Hahn et al.
2025
Hahn et al.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2025) 224 (7): e202408006.
Article history
Received:
August 02 2024
Revision Received:
February 28 2025
Accepted:
April 30 2025
Citation
Hye Jee Hahn, Natalya Pashkova, Michael A. Cianfrocco, Lois S. Weisman; Cargo adaptors use a handhold mechanism to engage with myosin V for organelle transport. J Cell Biol 7 July 2025; 224 (7): e202408006. doi: https://doi.org/10.1083/jcb.202408006
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