Control of Actin Ring Formation During Cell Division in Aspergillus

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9723711 Harris In preparation for cytokinesis, both animal and fungal cells assemble a cortical actin ring. The formation of this ring appears to be temporally and spatially controlled by signals from mitotic nuclei. Current models suggest that the actin ring functions via two possible mechanisms to effect cytokinesis. In animals and certain fungi, the actin ring contracts, splitting cells in two. In other fungi, the ring defines a region where a cell plate forms to divide the cell. Regardless of mechanism used, the actin ring is essential for cytokinesis. Previous studies employing various biochemical and genetic approaches have identified numerous proteins necessary for the formation and/or function of the actin ring. However, it is not at all clear how these proteins function in an integrated manner to control cytokinesis. Moreover, it has become increasingly evident that a complete inventory of actin ring proteins has not been attained. The overall objective of Dr. Harris' research program is to use the power of genetics to identify and characterize additional proteins required for the formation and function of the actin ring, and thereby elucidate the molecular mechanisms underlying cytokinesis in the genetically tractable filamentous fungus, Aspergillus nidulans. This fungus undergoes cytokinesis by forming crosswalls known as septa. Septum formation in A. nidulans is temporally and spatially coordinated with mitosis, and requires the formation of a contractile actin ring. Genetic screens have resulted in the identification and characterization of gene products which act at different steps to control septation in A. nidulans. For example, the analysis of sepB mutants has revealed the existence of a checkpoint which prevents septum formation in the presence of DNA damage. In contrast, the characterization of sepA mutants has led to the identification of an evolutionarily conserved protein that may control the assembly of the actin ring. The objective of this research project is to address the hypothesis that the sepA gene product plays an essential role in septum formation by promoting the formation of the contractile actin ring. Specifically, Dr. Harris will use indirect immunofluorescence to determine if SepA localizes to the incipient division site. In addition, he will establish the timing of SepA localization relative to mitosis and actin ring formation. He also plans to employ a battery of genetic and biochemical approaches to identify proteins that interact with SepA. In particular, he will test predictions that SepA function requires interactions with the actin-associated protein profilin and with the septins. The fascinating process of cytokinesis, in which a living cell literally separates itself into two progeny cells, underpins the nature of life. This research project should lead to a better understanding of the general mechanisms underlying cytokinesis. The use of a filamentous fungus as the model organism in this study is a particularly good choice because of the pronounced societal impact of fungi. On the one hand, some fungi cause diseases; on the other hand, they produce useful natural products such as antibiotics and commercially important enzymes, and can be genetically engineered to produce non-fungal proteins of commercial interest. Thus, an increased understanding of how septum formation permits filamentous fungi to grow and reproduce can lead to ways of combating fungal infections of plants, animals, and humans, as well as allowing fungi to be used more efficiently as industrial biocatalysts for the production of commercially important enzymes and other proteins. ***