P21-activated kinases role in epithelial morphogenesis and cytoskeletal polarity

Cell shape and cell movement play vital roles in organ formation and the sculpting of body shape in the development of multicellular organisms. The Rho family of small GTPases are key regulators of cell shape and cell movement through their participation in signaling pathways involved in a variety of cell processes. These proteins function as “molecular switches”, with the ability to alternate between active and inactive states. Malfunction of these switching mechanisms has been implicated in a variety of disorders including cancer, and a number of inherited conditions such as X-linked mental retardation and faciogenital dysplasia (Aarskog syndrome). These proteins have also been shown to be key regulators in wound healing. The p21-activated kinases (Paks) are proteins that have been shown to alter activity of the Rho GTPases Cdc42 and Rac, and are linked to the regulation of the actin cytoskeleton. Previous studies have demonstrated Pak’s function in the establishment of cell shape and movement via regulation of the actin cytoskeleton. However, the exact nature of Pak within the signaling cascade remains unclear. Ryan Conder’s recent studies have suggested a role for Pak in either the establishment or maintenance of specific membrane surfaces of a cell that are required for tumor suppressor proteins to position themselves properly. Using Drosophila (fruit fly) developmental processes as a model system, Ryan is studying the proteins involved in these signaling networks and establishing the mechanisms by which these developmental processes are regulated. He hopes that what he learns about these signaling pathways in Drosophila will shed light on their roles in human development and disease.