GSBS Dissertations and Theses

Approval Date

8-3-2016

Document Type

Doctoral Dissertation

Academic Program

Interdisciplinary Graduate Program

Department

Program in Molecular Medicine

First Thesis Advisor

Stephen Doxsey, PhD

Keywords

Heat-Shock Proteins, Cell Division, Cell Movement, Cell Polarity, Centrioles, Centrosome, Endosomes, Epithelial Cells, Microtubule-Organizing Center, Microtubules, Cenexin

Subjects

Dissertations, UMMS; Heat-Shock Proteins; Cell Division; Cell Movement; Cell Polarity; Centrioles; Centrosome; Endosomes; Epithelial Cells; Microtubule-Organizing Center; Microtubules

Abstract

Epithelial cells are necessary building blocks of the organs they line. Their apicalbasolateral polarity, characterized by an asymmetric distribution of cell components along their apical-basal axis, is a requirement for normal organ function. Although the centrosome, also known as the microtubule organizing center, is important in establishing cell polarity the mechanisms through which it achieves this remain unclear. It has been suggested that the centrosome influences cell polarity through microtubule cytoskeleton organization and endosome trafficking. In the first chapter of this thesis, I summarize the current understanding of the mechanisms regulating cell polarity and review evidence for the role of centrosomes in this process.

In the second chapter, I examine the roles of the mother centriole appendages in cell polarity during cell migration and cell division. Interestingly, the subdistal appendages, but not the distal appendages, are essential in both processes, a role they achieve through organizing centrosomal microtubules. Depletion of subdistal appendages disrupts microtubule organization at the centrosome and hence, affects microtubule stability. These microtubule defects affect centrosome reorientation and spindle orientation during cell migration and division, respectively. In addition, depletion of subdistal appendages affects the localization and dynamics of apical polarity proteins in relation to microtubule stability and endosome recycling. Taken together, our results suggest the mother centriole subdistal appendages play an essential role in regulating cell polarity. A discussion of the significance of these results is included in chapter three.

DOI

10.13028/M2QC73

Rights and Permissions

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

Available for download on Tuesday, August 22, 2017

Share

COinS