Abstract
Ageing and the mortality that ensues are sustainable for the species only if age is reset in newborns. In budding yeast, buds are made young whereas ageing factors, such as carbonylated proteins and DNA circles, remain confined to the ageing mother cell. The mechanisms of this confinement and their relevance are poorly understood. Here we show that a septin-dependent, lateral diffusion barrier forms in the nuclear envelope and limits the translocation of pre-existing nuclear pores into the bud. The retention of DNA circles within the mother cell depends on the presence of the diffusion barrier and on the anchorage of the circles to pores mediated by the nuclear basket. In accordance with the diffusion barrier ensuring the asymmetric segregation of nuclear age-determinants, the barrier mutant bud6Δ fails to properly reset age in buds. Our data involve septin-dependent diffusion barriers in the confinement of ageing factors to one daughter cell during asymmetric cell division.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Stewart, E. J., Madden, R., Paul, G. & Taddei, F. Aging and death in an organism that reproduces by morphologically symmetric division. PLoS Biol. 3 doi: 10.1371/journal.pbio.0030045 (2005)
Mortimer, R. K. & Johnston, J. R. Life span of individual yeast cells. Nature 183, 1751–1752 (1959)
Pruyne, D. & Bretscher, A. Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states. J. Cell Sci. 113, 365–375 (2000)
Barral, Y., Mermall, V., Mooseker, M. S. & Snyder, M. Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast. Mol. Cell 5, 841–851 (2000)
Barton, A. A. Some aspects of cell division in Saccharomyces cerevisiae . J. Gen. Microbiol. 4, 84–86 (1950)
Breitenbach, M. et al. in Model Systems in Aging (eds Nyström T. & Osiewacz, H. D.) 61–96 (Springer, 2003)
Sinclair, D., Mills, K. & Guarente, L. Aging in Saccharomyces cerevisiae . Annu. Rev. Microbiol. 52, 533–560 (1998)
Hartwell, L. H., Culotti, J., Pringle, J. R. & Reid, B. J. Genetic control of the cell division cycle in yeast. Science 183, 46–51 (1974)
Kennedy, B. K., Austriaco, N. R. & Guarente, L. Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span. J. Cell Biol. 127, 1985–1993 (1994)
Sinclair, D. A. & Guarente, L. Extrachromosomal rDNA circles – a cause of aging in yeast. Cell 91, 1033–1042 (1997)
Murray, A. W. & Szostak, J. W. Pedigree analysis of plasmid segregation in yeast. Cell 34, 961–970 (1983)
Falcon, A. A. & Aris, J. P. Plasmid accumulation reduces life span in Saccharomyces cerevisiae . J. Biol. Chem. 278, 41607–41617 (2003)
Lippincott-Schwartz, J., Snapp, E. & Kenworthy, A. Studying protein dynamics in living cells. Nature Rev. Mol. Cell Biol. 2, 444–456 (2001)
Deshaies, R. J. & Schekman, R. A yeast mutant defective at an early stage in import of secretory protein precursors into the endoplasmic reticulum. J. Cell Biol. 105, 633–645 (1987)
Flury, I. et al. INSIG: a broadly conserved transmembrane chaperone for sterol-sensing domain proteins. EMBO J. 24, 3917–3926 (2005)
Wente, S. R., Rout, M. P. & Blobel, G. A new family of yeast nuclear pore complex proteins. J. Cell Biol. 119, 705–723 (1992)
Beilharz, T., Egan, B., Silver, P. A., Hofmann, K. & Lithgow, T. Bipartite signals mediate subcellular targeting of tail-anchored membrane proteins in Saccharomyces cerevisiae . J. Biol. Chem. 278, 8219–8223 (2003)
Pelham, H. R. Recycling of proteins between the endoplasmic reticulum and Golgi complex. Curr. Opin. Cell Biol. 3, 585–591 (1991)
Megee, P. C. & Koshland, D. A functional assay for centromere-associated sister chromatid cohesion. Science 285, 254–257 (1999)
Daigle, N. et al. Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells. J. Cell Biol. 154, 71–84 (2001)
Belgareh, N. & Doye, V. Dynamics of nuclear pore distribution in nucleoporin mutant yeast cells. J. Cell Biol. 136, 747–759 (1997)
Bucci, M. & Wente, S. R. In vivo dynamics of nuclear pore complexes in yeast. J. Cell Biol. 136, 1185–1199 (1997)
Zabel, U. et al. Nic96p is required for nuclear pore formation and functionally interacts with a novel nucleoporin, Nup188p. J. Cell Biol. 133, 1141–1152 (1996)
Walther, T. C. et al. The conserved Nup107–160 complex is critical for nuclear pore complex assembly. Cell 113, 195–206 (2003)
Faty, M., Fink, M. & Barral, Y. Septins: a ring to part mother and daughter. Curr. Genet. 41, 123–131 (2002)
Haarer, B. K. & Pringle, J. R. Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck. Mol. Cell. Biol. 7, 3678–3687 (1987)
Amberg, D. C., Zahner, J. E., Mulholland, J. W., Pringle, J. R. & Botstein, D. Aip3p/Bud6p, a yeast actin-interacting protein that is involved in morphogenesis and the selection of bipolar budding sites. Mol. Biol. Cell 8, 729–753 (1997)
Mino, A. et al. Shs1p: a novel member of septin that interacts with spa2p, involved in polarized growth in Saccharomyces cerevisiae . Biochem. Biophys. Res. Commun. 251, 732–736 (1998)
Imamura, H. et al. Bni1p and Bnr1p: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae . EMBO J. 16, 2745–2755 (1997)
Scott-Drew, S., Wong, C. M. & Murray, J. A. DNA plasmid transmission in yeast is associated with specific sub-nuclear localisation during cell division. Cell Biol. Int. 26, 393–405 (2002)
Oakes, M. et al. Mutational analysis of the structure and localization of the nucleolus in the yeast Saccharomyces cerevisiae . J. Cell Biol. 143, 23–34 (1998)
Doye, V., Wepf, R. & Hurt, E. C. A novel nuclear pore protein Nup133p with distinct roles in poly(A)+ RNA transport and nuclear pore distribution. EMBO J. 13, 6062–6075 (1994)
Strambio-de-Castillia, C., Blobel, G. & Rout, M. P. Proteins connecting the nuclear pore complex with the nuclear interior. J. Cell Biol. 144, 839–855 (1999)
Sinclair, D. A., Mills, K. & Guarente, L. Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants. Science 277, 1313–1316 (1997)
Gillespie, C. S. et al. A mathematical model of ageing in yeast. J. Theor. Biol. 229, 189–196 (2004)
Defossez, P. A. et al. Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Mol. Cell 3, 447–455 (1999)
Gourlay, C. W. & Ayscough, K. R. A role for actin in aging and apoptosis. Biochem. Soc. Trans. 33, 1260–1264 (2005)
Navarro, C. L., Cau, P. & Levy, N. Molecular bases of progeroid syndromes. Hum. Mol. Genet. 15, R151–R161 (2006)
Scaffidi, P. & Misteli, T. Lamin A-dependent nuclear defects in human aging. Science 312, 1059–1063 (2006)
Luedeke, C. et al. Septin-dependent compartmentalization of the endoplasmic reticulum during yeast polarized growth. J. Cell Biol. 169, 897–908 (2005)
Guthrie, C. & Fink, G. R. Guide to Yeast Genetics and Molecular Biology (Academic Press, 1991)
Huh, W. K. et al. Global analysis of protein localization in budding yeast. Nature 425, 686–691 (2003)
Winzeler, E. A. et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999)
Longtine, M. S. et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae . Yeast 14, 953–961 (1998)
Kusch, J., Meyer, A., Snyder, M. P. & Barral, Y. Microtubule capture by the cleavage apparatus is required for proper spindle positioning in yeast. Genes Dev. 16, 1627–1639 (2002)
Dobbelaere, J., Gentry, M. S., Hallberg, R. L. & Barral, Y. Phosphorylation-dependent regulation of septin dynamics during the cell cycle. Dev. Cell 4, 345–357 (2003)
Dobbelaere, J. & Barral, Y. Spatial coordination of cytokinetic events by compartmentalization of the cell cortex. Science 305, 393–396 (2004)
Acknowledgements
We thank D. Barral and J. Sasse, P. Megee, D. Koschland, T. Lithgow, L. Guarente, V. Doye, E. Hurt and M. Winey for technical help and sharing reagents, D. Gerlich and C. Weirich for reading the manuscript, and the Barral, Meraldi and Gerlich labs for discussions. We acknowledge G. Csucs, J. Kusch and the Light Microscopy Center (LMC, ETH Zurich) for support with microscopy equipment and techniques. This work was supported by the ETH Zurich, and by a grant from the Swiss National Foundation to Y.B. and G.G.
Author Contributions Z.S. did most of the experiments and contributed to the data analysis and to the writing of the paper; S.B. contributed to the ageing experiments; S.B.F. contributed to the FLIP experiments; G.G. did the in silico modelling; and Y.B. had the idea for the project, contributed to the data analysis and wrote the paper.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Information 1
The file contains Figures S1-S7 and Legends; Supplementary Methods; Supplementary Movie legends and Supplementary Notes with additional references. (PDF 818 kb)
nature07121-s2.mov
The file contains Supplementary Movie 1 which shows a representative FLIP experiment on a Nup49-GFP cell. Note that none of the movies was treated to account for the photobleaching due to picture acquisition. Please always keep an eye on the control cell. (MOV 963 kb)
nature07121-s3.mov
The file contains Supplementary Movie 2 which shows FLIP experiment on a Nsg1-GFP cell. (MOV 1032 kb)
nature07121-s4.mov
The file contains Supplementary Movie 3 which shows FLIP experiment on a Sec61-GFP cell. (MOV 1346 kb)
nature07121-s5.mov
The file contains Supplementary Movie 4 which shows FLIP experiment on a NLS-GFP cell. (MOV 210 kb)
nature07121-s6.mov
The file contains Supplementary Movie 5 which shows FLIP experiment on a Prm3-GFP cell. (MOV 433 kb)
nature07121-s7.mov
The file contains Supplementary Movie 6 which shows FLIP experiment on a GFP-HDEL cell. (MOV 869 kb)
nature07121-s8.mov
The file contains Supplementary Movie 7 which shows FRAP experiment on a Nup49-GFP cell. (MOV 1467 kb)
nature07121-s9.mov
The file contains Supplementary Movie 8 which shows FLIP experiment on a cdc12-6 Nsg1-GFP cell. (MOV 1280 kb)
nature07121-s10.mov
The file contains Supplementary Movie 9 which shows FLIP experiment on a bud6Δ Nsg1-GFP cell. (MOV 940 kb)
nature07121-s11.mov
The file contains Supplementary Movie 10 which shows CEN- pPCM14 plasmids codiffusing with nuclear pore clusters in nup133Δ cells. (MOV 57 kb)
nature07121-s12.mov
The file contains Supplementary Movie 11 which shows movement of CEN- pPCM14 plasmids in a kar9Δ cell. Note that the plasmids can move freely between the two lobes of anaphase nucleus until the mitotic spindle realigns with the mother-bud axis and passes through the bud neck. (MOV 105 kb)
nature07121-s13.mov
The file contains Supplementary Movie 12 which shows movement of CEN- pPCM14 plasmids in a wild type cell. None of the two plasmids crosses the bud neck. (MOV 31 kb)
nature07121-s14.mov
The file contains Supplementary Movie 13 which shows movement of CEN- pPCM14 plasmids in a cdc12-6 cell. In this cell, 2 out of 4 plasmids segregate towards the bud. (MOV 70 kb)
Rights and permissions
About this article
Cite this article
Shcheprova, Z., Baldi, S., Frei, S. et al. A mechanism for asymmetric segregation of age during yeast budding. Nature 454, 728–734 (2008). https://doi.org/10.1038/nature07212
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature07212
This article is cited by
-
Intercellular trafficking via plasmodesmata: molecular layers of complexity
Cellular and Molecular Life Sciences (2021)
-
Vimentin protects differentiating stem cells from stress
Scientific Reports (2020)
-
Cell size sets the diameter of the budding yeast contractile ring
Nature Communications (2020)
-
The functional universe of membrane contact sites
Nature Reviews Molecular Cell Biology (2020)
-
The fitness cost of mismatch repair mutators in Saccharomyces cerevisiae: partitioning the mutational load
Heredity (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.