GSBS Dissertations and Theses

Approval Date

June 2004

Document Type

Doctoral Dissertation

Department

Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program

Subjects

SNARE Proteins; Cell Division; Cell Cycle Proteins; Centrioles; GTPase-Activating Proteins; Academic Dissertations; Dissertations, UMMS

Abstract

Although much progress has been made in understanding the events that lead to successful cell division, many details of this process remain a mystery. This dissertation presents findings which help to explain events that occur in the latest stages of cytokinesis, with an emphasis on the role of centrosome proteins. The first chapter introduces the novel centrosome protein centriolin. We show that this protein is localized specifically to the subdistal appendages of the maternal centriole in interphase, and it localizes to the midbody during cytokinesis. Disruption of this protein results in a unique cytokinesis defect in which cleavage furrow formation and ingression appear normal, but the cells remain connected by a thin intracellular bridge for extended periods of time. These results lead us to the conclusion that centriolin has an important function in cytokinesis. The second chapter describes our attempt to identify centriolin interacting partners. A yeast two hybrid screen was performed, and the results of this screen revealed an interaction between centriolin and proteins involved in vesicle target specificity and fusion. Further studies of these proteins revealed a novel localization to the midbody in cycling cells and a novel function in the final stages of cytokinesis, similar to centriolin. The third chapter discusses my attempts to clone and characterize a novel GTPase Activating Protein (GAP), which was also discovered in the screen for centriolin interacting proteins.

Comments

Some images did not scan well. Please consult original document.

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.