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Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole

Nature volume 422, pages 87–92 (2003)Cite this article

Abstract

Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments1,2,3. However, this alone does not determine the intracellular destination of organelles. For example, the yeast class V myosin, Myo2p, moves several organelles to distinct locations during the cell cycle4,5,6,7,8. Thus the movement of each type of Myo2p cargo must be regulated uniquely. Here we report a regulatory mechanism that specifically provides directionality to vacuole movement. The vacuole-specific Myo2p receptor, Vac17p, has a key function in this process. Vac17p binds simultaneously to Myo2p and to Vac8p, a vacuolar membrane protein. The transport complex, Myo2p–Vac17p–Vac8p, moves the vacuole to the bud, and is then disrupted through the degradation of Vac17p. The vacuole is ultimately deposited near the centre of the bud. Removal of a PEST sequence (a potential signal for rapid protein degradation) within Vac17p causes its stabilization and the subsequent ‘backward’ movement of vacuoles, which mis-targets them to the neck between the mother cell and the bud. Thus the regulated disruption of this transport complex places the vacuole in its proper location. This may be a general mechanism whereby organelles are deposited at their terminal destination.

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Figure 1: Vac17p is required for vacuole inheritance and forms a complex with Myo2p and Vac8p.
Figure 2: A block in vacuole inheritance or deletion of the Vac17p PEST sequence results in elevated levels of Vac17p.
Figure 4: Regulated degradation of Vac17p releases Myo2p and deposits the vacuoles in the bud.
Figure 3: Vac17p levels oscillate during the cell cycle.

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Acknowledgements

We thank M. Cantwell for helping with the isolation of the vac17-1 mutant. We thank T. Monniger and the University of Iowa Central Microscopy Research Facility for guidance in the use of the confocal microscope. We thank R. Cohen, J. Donelson, R. Piper, P. Rubenstein, J. Shaw and M. Stamnes for discussions. This work was supported by grants from the National Institutes of Health and the National Science Foundation (to L.S.W).

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Author notes

  1. Natalie L. Catlett

    Present address: Torrey Mesa Research Institute, Syngenta Research and Technology, 3115 Merryfield Row 100, San Diego, California, 92121, USA

  2. Lois S. Weisman: Correspondence and requests for materials should be addressed to L.S.W.

Authors and Affiliations

  1. Department of Biochemistry, University of Iowa, Iowa City, Iowa, 52242, USA

    Fusheng Tang, Emily J. Kauffman, Jennifer L. Novak, Johnathan J. Nau, Natalie L. Catlett & Lois S. Weisman

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Correspondence to Lois S. Weisman.

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Tang, F., Kauffman, E., Novak, J. et al. Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole. Nature 422, 87–92 (2003). https://doi.org/10.1038/nature01453

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