Date

8-9-2011

UMMS Affiliation

Graduate School of Biomedical Sciences, Interdisciplinary Graduate Program

Document Type

Dissertation, Doctoral

Subjects

Dissertations, UMMS; Cytokinesis

Disciplines

Cell and Developmental Biology | Life Sciences | Medicine and Health Sciences

Abstract

Cytokinesis is the final chapter of cell division and its last page is abscission, the physical separation of two daughter cells. During cytokinesis of vertebrate cells, two future daughter cells are connected by an intercellular bridge within which the midbody (MB) is positioned. Since becoming the focus of intense investigations on cytokinesis completion, MB is now perceived as a complicated organelle where multiple pathways for abscission are targeted and coordinated. However, whether post-mitotic midbodies, the midbody derivatives (MBds), would be retained by either daughter cell post-abscission remains unexplored. In addition, how cells manage the fate of inherited MBds is also unclear or only sketchily proposed. Finally, whether the inherited MBds in cells may play non-cytokinetic roles is also unaddressed.

In the first chapter, I review the historical and current understanding of MBs, with emphasis on their roles in cytokinesis whereas potential non-cytokinetic roles are also covered. In the second chapter, the aforementioned three questions are sequentially addressed. First, the newly-formed MBd appears to be inherited by the daughter cell with the older centrosome. Second, MBds are not only inherited but also accumulated in cancer and pluripotent stem cells, but not in normal somatic (differentiated) cells. In normal somatic cells, MBds are within membrane-bound compartments for lysosomemediated degradation via autophagosome engulfment. This partially explains why MBd-accumulation is rarely observed in these cells. In contrast to the previous model, colleagues and I showed that MBd-accumulation correlates well with the autophagosomal-lysosomal activity, but not with the proliferation rate. Finally, the experimental increase of MBd levels appears to enhance the anchorage-independent growth in cancer cells and the efficiency of reprogramming in fibroblasts. In the last chapter, I conclude our findings and discuss future directions in two aspects.

 
 

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