Mechanisms of cytokinesis in fission yeast

Life depends on the ability of cells to divide. Cytokinesis is the process by which one cell splits into two. The earliest microscopes revealed cell division to scientists in the early 19th century (Figure 1). We now know that cytokinesis in most eukaryotic cells relies on the assembly and constriction of an actin/myosin-based ring structure. However, many basic questions about how cytokinesis is orchestrated on a molecular level remain unanswered today.;My work addresses and advances our understanding of a few of these questions: (1) How is actin reorganized to form a contractile ring at the division plane? (2) Is cdc12p formin in the ring dynamic and how are ring dynamics controlled? (3) How is cytokinesis regulated to occur at the correct time in the cell cycle? (4) What are the sources of contractile force driving ring contraction and what is the role of myosin motor activity in cytokinesis?;Cytokinesis in the fission yeast Schizosaccharomyces pombe depends on the actin nucleating formin cdc12. In chapter one, I describe a mutational study characterizing the functions of specific regions or domains within the cdc12 protein in cytokinesis. These experiments have helped to clarify how actin filaments are assembled in the contractile ring and how actin assembly is appropriately localized in the cell. Chapter two describes cdc12p dynamics and observations of how formin-mediated actin assembly activity affects both actin and formin turnover within the ring. Chapter three covers efforts to understand how cdc12p is regulated. Through a characterization of a cdc12p mutant that induces cytokinesis at inappropriate times, I show that formin activity may be a pivotal target and coordinator of cell cycle control of cytokinesis. The final chapter includes a broad range of preliminary experiments that aimed to clarify the mechanics of ring contraction. A characterization of the effects of a chemical inhibitor of myosin shed light on the role of the myosin motor in both contraction and assembly of the ring.;Together, this work has touched on key questions in the field and elucidated important molecular details of cdc12 formin and myosin function in cytokinesis. Many aspects of cell division in fission yeast are conserved in metazoans, so these studies may lend broader insights into the mechanisms of cytokinesis in multi-cellular organisms.