Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2003.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2005
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| Online Access: | http://hdl.handle.net/1721.1/29364 |
| _version_ | 1826209157150146560 |
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| author | Shimoda, Soni Lacefield, 1976- |
| author2 | Frank Solomon. |
| author_facet | Frank Solomon. Shimoda, Soni Lacefield, 1976- |
| author_sort | Shimoda, Soni Lacefield, 1976- |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2003. |
| first_indexed | 2024-09-23T14:18:24Z |
| format | Thesis |
| id | mit-1721.1/29364 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T14:18:24Z |
| publishDate | 2005 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/293642019-04-11T06:10:48Z Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae Shimoda, Soni Lacefield, 1976- Frank Solomon. Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Dept. of Biology. Biology. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2003. Includes bibliographical references. Undimerized -tubulin is toxic to the yeast Saccharomyces cereivisiae. Free P-tubulin can arise if the tubulin heterodimer dissociates or if levels of 3-tubulin and cc-tubulin are unbalanced. I am using the toxicity of 3-tubulin to understand the early steps in microtubule morphogenesis. I have found that a mutation of the gene PLP1 allows cells to survive the toxicity of [3-tubulin produced from disparate levels of - and -tubulin. The suppression occurs either when c-tubulin is modestly underexpressed relative to -tubulin, or when 13-tubulin is inducibly and strongly overexpressed. A significant proportion of the undimerized -tubulin in plpl cells is less toxic and less functional than in wild type cells. As a result, piplA cells have lower levels of heterodimer. Significantly, plpl cells that also lack PaclOp, a component of the GimC/Pfd complex that helps fold tubulin polypeptides, are even less affected by free -tubulin. Our results suggest that Plplp defines a novel step in -tubulin folding. My work demonstrates an interaction between the pathways for tubulin folding and the regulation of tubulin expression. Cells that are paclOA piplA have much less folded and functional -tubulin than even plplA cells, and also upregulate -tubulin through increasing transcription. The upregulation of -tubulin RNA is dependent on the putative transcription factor Cin5p. In the absence of CIN5, paclO plpl A cells have decreased tubulin heterodimer levels, down to approximately 20% that of wild type. The heterodimer levels are also decreased from paclO plpl cells suggesting that the limiting factor in heterodimer formation in paclO plpl in5A is -tubulin. The paclOA plpl cin5 cells grow normally, but have mitotic defects such as abnormal nuclear positioning and short anaphase spindles. (cont.) The Cin5p dependent upregulation of 3-tubulin may be a mechanism to maintain tubulin heterodimer levels and so sustain normal microtubule function. by Soni Lacefield Shimoda. Ph.D. 2005-10-14T20:06:17Z 2005-10-14T20:06:17Z 2003 2003 Thesis http://hdl.handle.net/1721.1/29364 52806789 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 157 leaves 6016422 bytes 10982078 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Shimoda, Soni Lacefield, 1976- Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae |
| title | Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae |
| title_full | Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae |
| title_fullStr | Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae |
| title_full_unstemmed | Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae |
| title_short | Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae |
| title_sort | normal microtubule function and the interaction between the pathways for tubulin folding and expression in s cerevisiae |
| topic | Biology. |
| url | http://hdl.handle.net/1721.1/29364 |
| work_keys_str_mv | AT shimodasonilacefield1976 normalmicrotubulefunctionandtheinteractionbetweenthepathwaysfortubulinfoldingandexpressioninscerevisiae |