2026-09-19T21:11:28Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/293642022-01-13T07:54:15Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Frank Solomon.
Shimoda, Soni Lacefield, 1976-
Massachusetts Institute of Technology. Dept. of Biology.
Massachusetts Institute of Technology. Department of Biology
2005-10-14T20:06:17Z
2005-10-14T20:06:17Z
2003
2003
http://hdl.handle.net/1721.1/29364
52806789
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.
157 leaves
6016422 bytes
10982078 bytes
application/pdf
application/pdf
eng
Massachusetts Institute of Technology
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http://dspace.mit.edu/handle/1721.1/7582
Biology.
Normal microtubule function and the interaction between the pathways for tubulin folding and expression in S. cerevisiae
Thesis
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Publication
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<Abstract>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.</Abstract>
<Abstract>(cont.) The Cin5p dependent upregulation of 3-tubulin may be a mechanism to maintain tubulin heterodimer levels and so sustain normal microtubule function.</Abstract>
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