Date

September 2004

UMMS Affiliation

Graduate School of Biomedical Sciences

Document Type

Dissertation, Doctoral

Subjects

Cell Cycle Proteins; Cell Division; Centrosome; Cilia; Cytokinesis; Microtubule-Associated Proteins; Academic Dissertations; Dissertations, UMMS

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The work presented here describes novel functions for centrosome proteins, specifically for pericentrin and centriolin. The first chapter describes the involvement of pericentrin in ciliogenesis. Cells with reduced pericentrin levels were unable to form primary cilia in response to serum starvation. In addition we showed novel interactions between pericentrin, intraflagellar transport (IFT) proteins and polycystin 2 (PC2). Pericentrin was co-localized with IFT proteins and PC2 to the base of primary cilia and motile cilia. Ciliary function defects have been shown to be involved in many human diseases and IFT proteins and PC2 have been implicated in these diseases. We conclude that pericentrin is required for assembly of primary cilia possibly as an anchor for other proteins involved in primary cilia assembly. The second chapter describes identification of centriolin, a novel centriolar protein that localizes to subdistal appendages and is involved in cytokinesis and cell cycle progression. Depletion of centriolin leads to defects in the final stages of cytokinesis, where cells remain connected by thin intercellular bridges and are unable to complete abscission. The cytokinesis defects seemed to precede the G0/G1 p53 dependant cell cycle arrest. Finally, the third chapter is a continuation of the cytokinesis study and it identifies pericentrin as an interacting partner for centriolin. Like centriolin, pericentrin knockdown induces defects in the final stages of cytokinesis and leads to G0/G1 arrest. Moreover, pericentrin and centriolin interact biochemically and show codependency in their centrosome localization. We conclude that pericentrin and centriolin are members of the same pathway and are necessary for the final stages of cytokinesis.

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