The long term goals of this research are to determine how eukaryotic cells orient and position the contractile actin ring during cytokinesis. The precise orientation of cell division planes can impart different fates to daughter cells and is of fundamental importance to all eukaryotic cells. It has long been known that the ailment of the mitotic spindle dictates the axis of cleavage, however the mechanism by which the components of the mitotic spindle, namely the microtubules, communicates this information to the cell is unknown. We are studying the process in the fungus, Aspergillus nidulans. A. nidulans has a rich history as a model genetic organism for studies of mitosis and microtubule-mediated processes. The cells of A. nidulans are divided by crosswalls called septa and the process of septation involves a contractile acting ring whose formation is dependent on microtubules. Mutational analysis has been used to define a collection of genes required for septation. A group of these genes, sepH, sepD and sepG, appear to be specifically involved in actin ring formation and their function requires microtubules. The sepH gene encodes a protein kinase proposed to be involved in signaling actin ring formation. sepD and sepG are candidate genes for additional components of this signaling pathway.
The specific aims of this proposal are to identify the products of these genes and determine their biochemical role in actin ring formation. Specific probes will be developed to investigate actin ring formation in living cells. Novel genetic screens have been devised to identify additional components of this signaling pathway. The central hypothesis to be tested is that these genes represent part of conserved signaling pathway for actin ring formation.
|Bruno, K S; Morrell, J L; Hamer, J E et al. (2001) SEPH, a Cdc7p orthologue from Aspergillus nidulans, functions upstream of actin ring formation during cytokinesis. Mol Microbiol 42:3-12|
|Ye, X S; Lee, S L; Wolkow, T D et al. (1999) Interaction between developmental and cell cycle regulators is required for morphogenesis in Aspergillus nidulans. EMBO J 18:6994-7001|