The basal body is a microtubule-organizing center responsible for nucleating the cilium, a cellular structure important for a wide variety of cellular functions such as cell locomotion and sensing the surrounding environment. Defects in basal body function have been implicated in a number of human diseases such as polycystic kidney disease. Centrins are a ubiquitous family of small Ca2+ binding proteins at basal bodies. Structurally, they consist of two domains tethered by a short linker with each domain containing a pair of EF hands, a Ca2+ binding motif. Centrins are grouped into two groups based on sequence similarity to the human centrins, centrin 2 and centrin 3, and analyses of components that make up basal bodies in different species suggest that they contain a centrin isoform from each group. The functions and modes of actions for centrins are poorly understood despite their wide spread conservation at basal bodies across species. Key questions about centrins revolve around on what the functions of the two groups and are the two groups distinct, meaning do basal bodies require both centrin isoforms to function correctly. The ciliate protist Tetrahymena thermophila was used as a system to study centrin function at basal bodies. Tetrahymena contains two centrins at basal bodies, Cen1, the human centrin 2 homolog, and Cen2, the human centrin 3 homologue. Here, I have shown that both Cen1 and Cen2 function in basal body maintenance, orientation and separation. However, subsequent experiments have shown that the two proteins are quite distinct from each other, meaning that basal bodies require both centrin isoforms to function properly. I have further analyzed the roles of centrins' domains and found out that they are, too, distinct. The N-terminal domain is involved in basal body orientation whereas the C-terminal domain is involved in protein localization and maintenance.
|Advisor:||Winey, Mark, Goodrich, James|
|Commitee:||Falke, Joseph, Palmer, Amy, Voeltz, Gia|
|School:||University of Colorado at Boulder|
|School Location:||United States -- Colorado|
|Source:||DAI-B 75/02(E), Dissertation Abstracts International|
|Keywords:||Basal bodies, Calcium binding, Centrin, Cilia, Tetrahymena|
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