Cytokinesis is a process that occurs at the end of each mitotic cycle in which an actin-based structure known as the contractile ring, constricts the plasma membrane and divides the cytoplasm into two compartments. Despite it central importance, remarkably little is known about many aspects of this process. Unresolved issues include the signals that control the timing and position of the contractile ring, the mechanisms by which actin and other components are recruited to the contractile ring, and the manner in which mitosis and cytokines are coordinated. In addition, it is likely that many components of the contractile ring have not been identified. The metaphase furrows which form during the cortical divisions of the syncytial Drosophila embryo provide a model system in which to study cytokinesis. These transient actin-myosin based furrows ar analogous to the contractile rings of conventional dividing cells. As many components are conserved in the two structures, lessons learned from one system are likely to apply to the other. This system is amenable to molecular, genetic, biochemical, and cellular approaches. A growing collection of mutations (currently there are 7) identifies genes that are specifically required for metaphase furrow formation. This proposal primarily focuses on two of these genes, nuclear-fallout (nuf) and grapes (grp). nuf encodes a protein with extensive coiled coil domains and preliminary analysis indicates that it is required for the assembly of actin and myosin in the furrows. grp encodes is a serine-threonine kinase, and preliminary analysis indicates it is required for the assembly of myosin in the metaphase furrows. Our goals are to precisely define the in vivo functions of these proteins in the formation of the metaphase furrows and to elucidate the mechanisms by which they are carried out. In addition, this collection of 7 mutations provides a unique opportunity to analyze how the vents of metaphase furrow formation are coordinated.
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