Grant: Project Grant

Cells adopt different shapes to efficiently carry out specific functions. Cell shape changes are caused by rearranging internal networks of proteins collectively called the cytoskeleton. When the cytoskeleton adopts the wrong shape at the wrong time the cell cannot carry out its function. One important example in human disease is that disruption of the cytoskeleton disrupts cell division and can lead to tumors. Other cytoskeleton rearrangements are required for cell migration, important for metastasis, and the production of cilia, the cell's antennae which are needed for correct kidney function. Therefore understanding how the cytoskeleton is dynamically reorganized at the molecular level will provide new platforms for drug discovery and therapeutics to treat diseases such as cancer and ciliopathies. Our proposal focuses on the protein anillin that binds to and regulates the cytoskeleton. As anillin interacts with many cellular factors, we propose that anillin accepts different incoming cellular signals and translates them into changes in the cytoskeleton. We have discovered a new mechanism whereby anillin regulates the formation of new cytoskeletal elements during cell division. We propose to determine how this new process regulates cell shape changes during cell division and determine if this mechanism operates in other cell shape changes during cell migration. We have also made a new and exciting discovery that anillin is required for making cilia. When cilia are disrupted the cell cannot function and, especially in the kidney, this leads to disease. Mutations in anillin are linked to kidney disease and we will determine how anillin role in making cilia. We expect our studies to identify new regulatory mechanisms that control cell shape during cell division, cell migration and ciliogenesis. This information will be important for the development of new therapeutic strategies in human disease, in particular cancer.