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Dissertation
New understanding of the effects of microtubule-associated proteins on dynamic instability, including the role of tau in neuronal function and disease
Doctor of Philosophy (Ph.D.), Drexel University
May 2018
DOI:
https://doi.org/10.17918/D86Q28
Abstract
As morphologically complex and polarized structures, neurons are critically dependent on cytoskeletal function. Neuronal processes are formed and maintained on a backbone of microtubules, which not only act as a structural support for axonal growth and formation, but also play important roles through their dynamic instability. Proper microtubule function, and by extension axonal function, relies upon distinct sub-populations of highly dynamic and highly stable microtubules. The functional difference between these domains has increasingly been shown to play a role in how microtubules promote axonal growth and interact with microtubule-associated proteins. Current dogma suggests that microtubule degeneration in neurological disease may best be averted by using microtubule-stabilizing drugs. In contrast, we demonstrate how siRNA knockdown of Fidgetin, a protein that specifically severs unstable microtubules, can promote neuronal growth by enhancing labile microtubule mass. We also investigate the role of tau in microtubule dynamics, demonstrating that tau does not act as a stabilizer of microtubules but rather promotes the growth and retention of dynamic microtubules, while MAP6, another microtubule-associated protein with true stabilizing characteristics, acts in opposite fashion. These findings open a new path for research into the mechanisms of tau and the possibilities of using labile microtubule manipulation to treat disease.
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Details
- Title
- New understanding of the effects of microtubule-associated proteins on dynamic instability, including the role of tau in neuronal function and disease
- Creators
- Timothy Ottum Austin - DU
- Contributors
- Peter W. Baas (Advisor) - Drexel University (1970-)Timothy J. Cunningham (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vii, 82 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 7967; 991014632308304721