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. 1998 Jun;149(2):857–864. doi: 10.1093/genetics/149.2.857

Modulation of tubulin polypeptide ratios by the yeast protein Pac10p.

P Alvarez 1, A Smith 1, J Fleming 1, F Solomon 1
PMCID: PMC1460170  PMID: 9611197

Abstract

Normal assembly and function of microtubules require maintenance of the proper levels of several proteins, including the tubulin polypeptides themselves. For example, in yeast a significant excess of beta-tubulin causes rapid microtubule disassembly and subsequent cell death. Even the modest excess of beta-tubulin produced by genetic alterations such as deletion of the minor alpha-tubulin gene TUB3 affects cell growth and can confer microtubule phenotypes. We show here that the levels of the yeast protein Pac10p affect the relative levels of the tubulin polypeptides. Cells deleted for PAC10 have the same phenotypes as do cells that express reduced levels of alpha-tubulin or Rbl2p, two proteins that bind beta-tubulin. Conversely, overexpression of Pac10p enhances the ability of alpha-tubulin or Rbl2p to suppress the lethality associated with excess beta-tubulin. However, Pac10p is itself not a beta-tubulin binding protein. Pac10 null cells show a 30% decrease in the ratio of alpha-tubulin to beta-tubulin. The results suggest that Pac10p modulates the level of alpha-tubulin in the cell, and so influences microtubule morphogenesis and tubulin metabolism.

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Selected References

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  1. Archer J. E., Vega L. R., Solomon F. Rbl2p, a yeast protein that binds to beta-tubulin and participates in microtubule function in vivo. Cell. 1995 Aug 11;82(3):425–434. doi: 10.1016/0092-8674(95)90431-x. [DOI] [PubMed] [Google Scholar]
  2. Campo R., Fontalba A., Sanchez L. M., Zabala J. C. A 14 kDa release factor is involved in GTP-dependent beta-tubulin folding. FEBS Lett. 1994 Oct 17;353(2):162–166. doi: 10.1016/0014-5793(94)01036-6. [DOI] [PubMed] [Google Scholar]
  3. Chen X., Sullivan D. S., Huffaker T. C. Two yeast genes with similarity to TCP-1 are required for microtubule and actin function in vivo. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9111–9115. doi: 10.1073/pnas.91.19.9111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Floor E. Interaction of morphogenetic genes of bacteriophage T4. J Mol Biol. 1970 Feb 14;47(3):293–306. doi: 10.1016/0022-2836(70)90303-7. [DOI] [PubMed] [Google Scholar]
  5. Gao Y., Melki R., Walden P. D., Lewis S. A., Ampe C., Rommelaere H., Vandekerckhove J., Cowan N. J. A novel cochaperonin that modulates the ATPase activity of cytoplasmic chaperonin. J Cell Biol. 1994 Jun;125(5):989–996. doi: 10.1083/jcb.125.5.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gao Y., Vainberg I. E., Chow R. L., Cowan N. J. Two cofactors and cytoplasmic chaperonin are required for the folding of alpha- and beta-tubulin. Mol Cell Biol. 1993 Apr;13(4):2478–2485. doi: 10.1128/mcb.13.4.2478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Geiser J. R., Schott E. J., Kingsbury T. J., Cole N. B., Totis L. J., Bhattacharyya G., He L., Hoyt M. A. Saccharomyces cerevisiae genes required in the absence of the CIN8-encoded spindle motor act in functionally diverse mitotic pathways. Mol Biol Cell. 1997 Jun;8(6):1035–1050. doi: 10.1091/mbc.8.6.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hoyt M. A., Macke J. P., Roberts B. T., Geiser J. R. Saccharomyces cerevisiae PAC2 functions with CIN1, 2 and 4 in a pathway leading to normal microtubule stability. Genetics. 1997 Jul;146(3):849–857. doi: 10.1093/genetics/146.3.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kirkpatrick D., Solomon F. Overexpression of yeast homologs of the mammalian checkpoint gene RCC1 suppresses the class of alpha-tubulin mutations that arrest with excess microtubules. Genetics. 1994 Jun;137(2):381–392. doi: 10.1093/genetics/137.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liu H., Krizek J., Bretscher A. Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Genetics. 1992 Nov;132(3):665–673. doi: 10.1093/genetics/132.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Melki R., Rommelaere H., Leguy R., Vandekerckhove J., Ampe C. Cofactor A is a molecular chaperone required for beta-tubulin folding: functional and structural characterization. Biochemistry. 1996 Aug 13;35(32):10422–10435. doi: 10.1021/bi960788r. [DOI] [PubMed] [Google Scholar]
  12. Schatz P. J., Pillus L., Grisafi P., Solomon F., Botstein D. Two functional alpha-tubulin genes of the yeast Saccharomyces cerevisiae encode divergent proteins. Mol Cell Biol. 1986 Nov;6(11):3711–3721. doi: 10.1128/mcb.6.11.3711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schatz P. J., Solomon F., Botstein D. Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins. Mol Cell Biol. 1986 Nov;6(11):3722–3733. doi: 10.1128/mcb.6.11.3722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schatz P. J., Solomon F., Botstein D. Isolation and characterization of conditional-lethal mutations in the TUB1 alpha-tubulin gene of the yeast Saccharomyces cerevisiae. Genetics. 1988 Nov;120(3):681–695. doi: 10.1093/genetics/120.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sternberg N. A genetic analysis of bacteriophage lambda head assembly. Virology. 1976 Jun;71(2):568–582. doi: 10.1016/0042-6822(76)90382-2. [DOI] [PubMed] [Google Scholar]
  16. Sternlicht H., Farr G. W., Sternlicht M. L., Driscoll J. K., Willison K., Yaffe M. B. The t-complex polypeptide 1 complex is a chaperonin for tubulin and actin in vivo. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9422–9426. doi: 10.1073/pnas.90.20.9422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tian G., Huang Y., Rommelaere H., Vandekerckhove J., Ampe C., Cowan N. J. Pathway leading to correctly folded beta-tubulin. Cell. 1996 Jul 26;86(2):287–296. doi: 10.1016/s0092-8674(00)80100-2. [DOI] [PubMed] [Google Scholar]
  18. Tian G., Lewis S. A., Feierbach B., Stearns T., Rommelaere H., Ampe C., Cowan N. J. Tubulin subunits exist in an activated conformational state generated and maintained by protein cofactors. J Cell Biol. 1997 Aug 25;138(4):821–832. doi: 10.1083/jcb.138.4.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ursic D., Culbertson M. R. The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes. Mol Cell Biol. 1991 May;11(5):2629–2640. doi: 10.1128/mcb.11.5.2629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weinstein B., Solomon F. Microtubule assembly and phage morphogenesis: new results and classical paradigms. Mol Microbiol. 1992 Mar;6(6):677–681. doi: 10.1111/j.1365-2958.1992.tb01515.x. [DOI] [PubMed] [Google Scholar]
  21. Weinstein B., Solomon F. Phenotypic consequences of tubulin overproduction in Saccharomyces cerevisiae: differences between alpha-tubulin and beta-tubulin. Mol Cell Biol. 1990 Oct;10(10):5295–5304. doi: 10.1128/mcb.10.10.5295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yaffe M. B., Farr G. W., Miklos D., Horwich A. L., Sternlicht M. L., Sternlicht H. TCP1 complex is a molecular chaperone in tubulin biogenesis. Nature. 1992 Jul 16;358(6383):245–248. doi: 10.1038/358245a0. [DOI] [PubMed] [Google Scholar]

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