This project characterizes CENP-F protein function at a cellular and organ level. First, I outline our plan used to identify novel binding partners. The first binding partner I describe is syntaxin 4 and the interaction between CENP-F and this SNARE protein regulates vesicular transport along the microtubule network. Second, I discuss the binding of CENP-F and Hook2, a centrosomal protein, and the role of CENP-F in centrosomal microtubule nucleation. Additionally, novel immunohistochemical and gene ablation reagents were developed to complete these studies. These two binding partners both illustrate a vital role of CENP-F with the microtubule network throughout the cell. To introduce our model of organogenesis, I outline the process of heart development, with emphasis on the avian model. Given the dynamic and high expression of CENP-F in this vital organ, it is an excellent model in which to study the role of CENP-F in vivo. Finally, I report our initial findings with the heart-specific deletion of CENP-F in the mouse. The ablation of CENP-F in developing cardiomyocytes leads to a small heart with thinner walls that develops progressive dilated cardiomyopathy and irregular conduction patterns. Investigations into the underlying function that is disrupted the CENP-F-/- hearts resulting in these phenotypes are ongoing. Overall, this thesis characterizes the function of CENP-F via binding partner identification and disruption of protein function using cell biological methodologies and genetic deletion. These approaches elucidate function with the microtubule network in vesicular transport and centrosomal microtubule nucleation and show an important role in normal murine heart development.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12012009-163833 |
| Date | 07 December 2009 |
| Creators | Moynihan, Katherine Lynn |
| Contributors | Maureen Gannon, Irina Kaverina, Patricia Labosky, David Bader, Vivien Casagrande |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12012009-163833/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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