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Organelles on the move: insights from yeast vacuole inheritance

Key Points

  • Organelle inheritance is one of several processes that occur during cell division and is an intrinsic part of the cell cycle. Recent studies on vacuole inheritance in the yeast Saccharomyces cerevisiae have indicated rules that probably apply to most organelle-inheritance pathways.

  • These rules include the fact that organelle inheritance is spatially controlled — organelles are targeted to the correct location in daughter cells — and that organelle inheritance is precisely coordinated with the cell cycle.

  • The S. cerevisiae vacuole moves using a myosin-V motor, Myo2, which is found in almost all eukaryotes. Including the vacuole, Myo2 can move at least six distinct cargoes, and it is linked to its cargoes through cargo-specific receptors.

  • Myo2 attaches to the vacuole through interactions with Vac17, which, in turn, interacts with the vacuole membrane protein Vac8. Together, these proteins link Myo2 to the vacuole, and they also have regulatory roles in vacuole inheritance.

  • The regulation of Vac17 turnover has a role in placing the vacuole in the correct cellular location. In addition, the regulation of VAC17 transcription probably coordinates vacuole inheritance with the cell cycle. Vac8 has several vacuole-related functions, so it might coordinate vacuole inheritance with other vacuole processes.

  • Genetic studies have shown that the signalling lipid phosphatidylinositol-3,5-bisphosphate is required for vacuole inheritance. It seems to function in the fission of the vacuole segregation structure, which terminates vacuole inheritance. It might also function in the initiation of vacuole inheritance through a role in the formation of the tubules that make up the vacuole segregation structure.

Abstract

Organelle inheritance is one of several processes that occur during cell division. Recent studies on yeast vacuole inheritance have indicated rules that probably apply to most organelle-inheritance pathways. They have uncovered a molecular mechanism for membrane-cargo transport that is partially conserved from yeast to humans. They have also shown that the transport complex, which is composed of a molecular motor and its receptor, regulates the destination and timing of vacuole movement and might coordinate organelle movement with several other organelle functions.

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Figure 1: Vacuole inheritance in a yeast zygote.
Figure 2: Schematic diagram of some of the proteins that are required for vacuole inheritance.
Figure 3: Schematic diagrams of Myo2.
Figure 4: Location of patches of highly conserved amino acids on the surface of the Myo2 globular tail.
Figure 5: Comparison of two organelle-specific myosin-V transport complexes.
Figure 6: Model of the molecular basis of yeast vacuole inheritance.
Figure 7: Vac8 coordinates vacuole inheritance with several diverse vacuole-related processes.

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Acknowledgements

I would like to thank the members of my laboratory for comments on this manuscript. Our research on vacuole inheritance is currently supported by the National Institutes of Health.

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Supplementary information S1

Vacuole inheritance in a yeast zygote (MOV 2779 kb)

The Saccharomyces cerevisiae zygote shown originated from the fusion of two haploid S. cerevisiae cells of opposite mating types. The vacuoles of one haploid mother cell (bottom) were fluorescently labelled, so the itinerary of vacuoles that were derived from this mother cell could be observed. In the strain used in this study, vacuole inheritance occurs after bud formation, which enables bud emergence and vacuole inheritance to be viewed separately. Vesicular–tubular projections that are known as segregation structures extend from the mother vacuole and rapidly migrate into the bud (middle right). More than one structure can form from the mother vacuole. The structures emerge from a region of the vacuole that is closest to the bud and they emerge from both parental vacuoles. The parental vacuoles never fuse, but the segregation structures fuse in the bud. Once fusion occurs, the vacuole contents move through the segregation structures from the mother to the bud vacuole and also from the bud back to the mother vacuole, which results in the appearance of fluorophore in the originally unlabelled mother vacuole (top). The original images were acquired at a rate of 1 per 7 seconds, and the movie plays 22 times faster than the acquisition rate. This movie was kindly provided by B. Getting (Terra Firma Design and Consulting, Steamboat Springs, Colorado, USA).

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DATABASES

Saccharomyces genome database

Atg13

Atg18

Bim1

Fab1

Fig4

Inp1/Ymr204

Kar9

Myo2

Myo4

Nvj1

Vac7

Vac8

Vac14

Vac17

Vps21/Ypt5

FURTHER INFORMATION

Lois Weisman's laboratory

Glossary

Yeast vacuole

An endocytic organelle that is equivalent to the plant vacuole and the mammalian lysosome. It is important in ion and water homeostasis, the storage of metabolites, and is an important site for protein turnover.

Yeast zygote

When two haploid yeast cells of opposite mating types fuse, the resulting binucleate cell is the zygote. However, for the purposes of this review, the term zygote is used to refer to a cell that is formed from two haploid cells both before and after nuclear fusion.

Mating types

Both haploid and diploid yeast can propagate by vegetative growth. Haploid cells can have one of two mating types. Haploid yeast of opposite mating types fuse to form diploid cells, whereas haploid yeast of the same mating type do not fuse.

Myosin-V motor

Myosins are classified according to their protein sequence. Myosin-V motors are found in virtually all eukaryotes and function in relatively long-range actin-based movements.

IQ motif

A small structural domain with the sequence (FILV)QXXX(RK)-GXXX(RK)XX(FILVWY) (residues in brackets can substitute for each other and X can be any amino acid). It generally binds to calmodulin, but can bind to other regulatory proteins.

Light chain

The regulatory light chains of myosin-V motors modulate myosin-V function. The regulatory light chains of the yeast myosin V Myo2 are calmodulin (a Ca2+-binding protein that regulates many Ca2+-mediated events) and myosin light chain-1 (Mlc1).

Cortical endoplasmic reticulum

(cortical ER). The ER in yeast is an extension of the outer membrane of the nucleus, and most of it surrounds the nucleus. However, some of it branches out and contacts the plasma membrane, and the branches that are adjacent to the plasma membrane are referred to as cortical ER.

Rab GTPases

Rab GTPases belong to the Ras superfamily of small (approximately 20 kDa) GTPases. Through their interactions with specific proteins, Rab GTPases regulate vesicle formation, membrane fusion and selected actin- and tubulin-dependent molecular motors.

Geranylgeranylation

The post-translational modification of a protein with geranylgeranyl — a C20 isoprenoid lipid. Rab GTPases are geranylgeranylated.

G1 cyclin

Cyclins are the regulatory subunits of cyclin-dependent kinases (CDKs), and a CDK generally interacts with more than one type of cyclin. CDKs are present throughout the cell cycle, whereas their cyclin regulators are present at a specific time in the cell cycle, for example, in G1 phase.

Macroautophagy

One of several pathways that occur in eukaryotic cells and function in the turnover of cellular components. A double-membrane vesicle is formed around an organelle and/or a portion of the cytoplasm. This vesicle is then targeted to the lysosome/vacuole, where the contents are degraded.

Interphase

The period of the cell cycle during which the cell is not actively dividing.

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Weisman, L. Organelles on the move: insights from yeast vacuole inheritance. Nat Rev Mol Cell Biol 7, 243–252 (2006). https://doi.org/10.1038/nrm1892

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