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The yeast gene, MDM20, is necessary for mitochondrial inheritance and organization of the actin cytoskeleton.

Hermann GJ, King EJ, Shaw JM - J. Cell Biol. (1997)

Bottom Line: Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process.Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents.Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City 84112, USA.

ABSTRACT
In Saccharomyces cerevisiae, the growing bud inherits a portion of the mitochondrial network from the mother cell soon after it emerges. Although this polarized transport of mitochondria is thought to require functions of the cytoskeleton, there are conflicting reports concerning the nature of the cytoskeletal element involved. Here we report the isolation of a yeast mutant, mdm20, in which both mitochondrial inheritance and actin cables (bundles of actin filaments) are disrupted. The MDM20 gene encodes a 93-kD polypeptide with no homology to other characterized proteins. Extra copies of TPM1, a gene encoding the actin filament-binding protein tropomyosin, suppress mitochondrial inheritance defects and partially restore actin cables in mdm20 delta cells. Synthetic lethality is also observed between mdm20 and tpm1 mutant strains. Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant phenotypes in the mdm20 strain to a lesser extent. Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process. MDM20 and TPM1 also exhibit the same pattern of genetic interactions; mutations in MDM20 are synthetically lethal with mutations in BEM2 and MYO2 but not SAC6. Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents. Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton.

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Summary of the synthetic interactions that involve  mdm20. The synthetic interactions between tpm1 and bem2 (Wang  and Bretscher, 1995), myo2 (Liu and Bretscher, 1992), and tpm2  (Drees et al., 1995) were previously reported.
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Figure 8: Summary of the synthetic interactions that involve mdm20. The synthetic interactions between tpm1 and bem2 (Wang and Bretscher, 1995), myo2 (Liu and Bretscher, 1992), and tpm2 (Drees et al., 1995) were previously reported.

Mentions: Some of our studies suggest that Tpm1p and Mdm20p might perform overlapping functions required for the integrity of the actin cytoskeleton. The disruption of both genes causes a similar loss of actin cables in cells and combinations of mutations in MDM20 and TPM1 result in synthetic lethality. In addition, like tpm1, mdm20 exhibits synthetic growth defects in combination with mutations in either BEM2 or MYO2 but not SAC6 (Fig. 8). Furthermore, we observe that overexpression of Tpm1p restores actin cables and rescues mitochondrial inheritance defects in mdm20. However, this suppression is not reciprocal; overexpression of Mdm20p does not rescue mutant phenotypes in tpm1 cells, suggesting that their roles in organizing actin differ. Mdm20p and Tpm1p do not appear to be structurally homologous since their amino acid sequences and sizes are quite different. If Mdm20p and Tpm1p do not have redundant functions, then an alternative explanation for the rescue of mdm20 mutant phenotypes by overexpressed Tpm1p is required. One possibility is that the overexpression of Tpm1p leads to the global stabilization of all actin filaments and cables in mdm20 cells, including those necessary for mitochondrial transport and inheritance. In support of this model, overexpression of Tpm1p is reported to cause more prominent cables and actin networks in wild-type cells and can restore actin cables in act1-2 mutant strains (Liu and Bretscher, 1989). Although overexpression of Tpm2p also suppresses mutant phenotypes in mdm20, we did not observe synthetic lethality in mdm20 tpm2 double mutants. Previous studies showed that the level of Tpm2p expression in wild-type cells is much lower than that of Tpm1p, and that cells lacking TPM2 do not exhibit defects in actin organization or growth (Drees et al., 1995). Thus, mdm20Δ tpm2Δ cells may contain enough Tpm1p to compensate for the loss of Tpm2p and prevent the cell death observed in mdm20Δ tpm1Δ double mutants.


The yeast gene, MDM20, is necessary for mitochondrial inheritance and organization of the actin cytoskeleton.

Hermann GJ, King EJ, Shaw JM - J. Cell Biol. (1997)

Summary of the synthetic interactions that involve  mdm20. The synthetic interactions between tpm1 and bem2 (Wang  and Bretscher, 1995), myo2 (Liu and Bretscher, 1992), and tpm2  (Drees et al., 1995) were previously reported.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139847&req=5

Figure 8: Summary of the synthetic interactions that involve mdm20. The synthetic interactions between tpm1 and bem2 (Wang and Bretscher, 1995), myo2 (Liu and Bretscher, 1992), and tpm2 (Drees et al., 1995) were previously reported.
Mentions: Some of our studies suggest that Tpm1p and Mdm20p might perform overlapping functions required for the integrity of the actin cytoskeleton. The disruption of both genes causes a similar loss of actin cables in cells and combinations of mutations in MDM20 and TPM1 result in synthetic lethality. In addition, like tpm1, mdm20 exhibits synthetic growth defects in combination with mutations in either BEM2 or MYO2 but not SAC6 (Fig. 8). Furthermore, we observe that overexpression of Tpm1p restores actin cables and rescues mitochondrial inheritance defects in mdm20. However, this suppression is not reciprocal; overexpression of Mdm20p does not rescue mutant phenotypes in tpm1 cells, suggesting that their roles in organizing actin differ. Mdm20p and Tpm1p do not appear to be structurally homologous since their amino acid sequences and sizes are quite different. If Mdm20p and Tpm1p do not have redundant functions, then an alternative explanation for the rescue of mdm20 mutant phenotypes by overexpressed Tpm1p is required. One possibility is that the overexpression of Tpm1p leads to the global stabilization of all actin filaments and cables in mdm20 cells, including those necessary for mitochondrial transport and inheritance. In support of this model, overexpression of Tpm1p is reported to cause more prominent cables and actin networks in wild-type cells and can restore actin cables in act1-2 mutant strains (Liu and Bretscher, 1989). Although overexpression of Tpm2p also suppresses mutant phenotypes in mdm20, we did not observe synthetic lethality in mdm20 tpm2 double mutants. Previous studies showed that the level of Tpm2p expression in wild-type cells is much lower than that of Tpm1p, and that cells lacking TPM2 do not exhibit defects in actin organization or growth (Drees et al., 1995). Thus, mdm20Δ tpm2Δ cells may contain enough Tpm1p to compensate for the loss of Tpm2p and prevent the cell death observed in mdm20Δ tpm1Δ double mutants.

Bottom Line: Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process.Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents.Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City 84112, USA.

ABSTRACT
In Saccharomyces cerevisiae, the growing bud inherits a portion of the mitochondrial network from the mother cell soon after it emerges. Although this polarized transport of mitochondria is thought to require functions of the cytoskeleton, there are conflicting reports concerning the nature of the cytoskeletal element involved. Here we report the isolation of a yeast mutant, mdm20, in which both mitochondrial inheritance and actin cables (bundles of actin filaments) are disrupted. The MDM20 gene encodes a 93-kD polypeptide with no homology to other characterized proteins. Extra copies of TPM1, a gene encoding the actin filament-binding protein tropomyosin, suppress mitochondrial inheritance defects and partially restore actin cables in mdm20 delta cells. Synthetic lethality is also observed between mdm20 and tpm1 mutant strains. Overexpression of a second yeast tropomyosin, Tpm2p, rescues mutant phenotypes in the mdm20 strain to a lesser extent. Together, these results provide compelling evidence that mitochondrial inheritance in yeast is an actin-mediated process. MDM20 and TPM1 also exhibit the same pattern of genetic interactions; mutations in MDM20 are synthetically lethal with mutations in BEM2 and MYO2 but not SAC6. Although MDM20 and TPM1 are both required for the formation and/or stabilization of actin cables, mutations in these genes disrupt mitochondrial inheritance and nuclear segregation to different extents. Thus, Mdm20p and Tpm1p may act in vivo to establish molecular and functional heterogeneity of the actin cytoskeleton.

Show MeSH
Related in: MedlinePlus