Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 71-83). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 71-83). Also available on the Internet.

Thesis (doctoral)--Universiteit van Amsterdam, 1990. / Includes bibliographical references.

Thesis (M.S.)--Brigham Young University. Dept. of Chemistry and Biochemistry, 2006. / Includes bibliographical references (p. 27-30).

Thesis (Ph. D.)--Ohio State University, 2005. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 September 20

Thesis (Ph.D.)--McMaster University, 2003. / Advisor: David W. Andrews. Includes bibliographical references (leaves 122-141) Also available via World Wide Web.

xiii, 48 p. : (col. ill.) A print copy of this title is available through the UO Libraries under the call number: SCIENCE QL537.D76 N57 2007 / Asymmetric cell division (ACD) is a unique mechanism employed during development to achieve cellular diversity from a small number of progenitor cells. Cells undergoing ACD distribute factors for self-renewal at the apical cortex and factors for differentiation at the basal cortex. It is critical for proper development that the mitotic spindle be tightly coupled to this axis of polarization such that both sets of proteins are exclusively segregated into the daughter cells. We use ACD in Drosophila neuroblasts as a model system for understanding the molecular mechanisms that govern spindle-cortical coupling. Neuroblasts polarize Partner of Inscuteable (Pins), Gαi and Mushroom Body Defect (Mud) at the apical cell cortex during mitosis. Gαi and Pins are required for establishing cortical polarity while Mud is essential for spindle-cortical alignment. Gαi and Mud interact through Pins GoLoco domains and tetratricopeptide repeats (TPR) respectively, however it is unclear how Mud activity is integrated with Pins and Gαi to link neuroblast cortical polarity to the mitotic spindle. This dissertation describes how Pins interactions with Gαi and Mud regulate Iwo fundamental aspects of neuroblast ACD: cortical polarity and alignment of the spindle with the resulting polarity axis. I demonstrate that Pins is a dynamic scaffolding protein that undergoes a GoLoco-TPR intramolecular interaction, resulting in a conformation of Pins with low Mud and reduced Gαi binding affinity. However, Pins TPR domains fail to completely repress Gαi binding, as a single GoLoco is unaffected by the intramolecular isomerization. Gαi present at the apical cortex specifies Pins localization through binding this "unregulated" GoLoco. Liberation of Pins intramolecularly coupled state occurs through cooperative binding of Gαi and Mud to the other GoLoco and TPR domains, creating a high-affinity Gαi-Pins-Mud complex. This autoregulatory mechanism spatially confines the Pins-Mud interaction to the apical cortex and facilitates proper apical-spindle orientation. In conclusion, these results suggest Gαi induces multiple Pins states to both properly localize Pins and ensure tight coupling between apical polarity and mitotic spindle alignment. / Adviser: Ken Prehoda

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Cysteinyl leukotriene receptor 2, a G-protein coupled receptor known to be expressed and functional on human platelets. However, it seems that upon ligand activation the cysteinyl leukotriene receptor 2 activates a variety of signaling pathways in multiple cell types among different species. Previously, a former laboratory member Vrinda Kulkarni found cysteinyl leukotriene receptor 2 to be expressed on the surface of adult zebrafish thrombocytes. In this work I studied the characteristics of aggregation in adult zebrafish thrombocytes with the knockdown of cysteinyl leukotriene receptor 2. I used a newly developed knockdown method to study the function of cysteinyl leukotriene receptor 2. Knockdown of the cysteinyl leukotriene was confirmed using RT-PCR results showed p=.001, reduced sell surface level of expression of the cysteinyl leukotriene receptor 2 results showed that p=.002. I found that the knockdown of cysteinyl leukotriene receptor 2 results in prothrombotic thrombocytes by using flow cytometry p=.0001.

Many Proteins require the aid of molecular chaperones to achieve a stable folding state and avoid misfolding pathologies. A major eukaryotic chaperone is the cytosolic chaperonin CCT. While CCT is known to fold a significant portion of all cytosolic proteins, there is no general model for the mechanism CCT uses to fold substrate proteins. One class of proteins that CCT is known to fold are β-propeller containing proteins. Here, we present structural and biochemical data on the processes that CCT uses to fold three distinct β-propeller proteins: the G-protein Beta 5 (Gβ5) subunit of the Gβ5-RGS complex, mLST8 of the mTOR complexes, and BBS2, 7, and 9 of the BBSome. We also explore the mechanisms by which these proteins are assembled into their respective signaling complexes after being folded by CCT. We found that each CCT substrate follows a unique folding trajectory and posit that the major determinants underlying each trajectory are governed by interactions between the substrate and CCT and interactions with downstream binding partners.