Assembly and Placement of the Cell Division Ring

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DESCRIPTION (provided by applicant): Interactions between microtubules and actin are critical for proper spatial organization in cells. During cytokinesis in animal cells, microtubules of the mitotic spindle position the cell division plane. Similar interactions between microtubules and actin also appear to regulate cell polarity and cell migration. The molecular mechanisms for these interactions are unknown. We study spatial regulation in the fission yeast Schizosaccharomyces pombe, a rod-shaped cell that grows from the cell tips and divides in the middle. The goal of this work is to determine how the sites of cell division and cell growth are positioned in the cell. Our preliminary results suggest that cell polarity and cytokinesis are regulated by particles that move to the cell tips or to the cell middle, dock at the plasma membrane, and then function to induce assembly of actin structures (actin cables for cell growth or the contractile actin ring for cytokinesis). In this grant, we propose to study these key motile particles: how do they move to specific locations in the cell, what are their molecular compositions and what are their functions? Our specific aims are: 1) to determine how plus-ends of microtubules deposit a particle containing the cell polarity factor tea1p at the cell tips; 2) to determine how tea1p functions at the cell tip to recruit a "polarisome" protein complex that assembles actin cables; 3) to determine how microtubules and actin target a motile particle containing the cytokinesis factor cdc12p to the future cell division site at the middle of the cell. These studies will elucidate a molecular mechanism for how microtubules regulate the spatial distribution of actin. As many of the proteins in these processes are conserved, this work will be directly relevant to general mechanisms of cell polarity and cell division that will be important for understanding development and human diseases such as cancer.