Regulation of dictyostelium type 1 myosins

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Movement is one of the fundamental properties of living cells. We are studying an amoeba, Dictyostelium discoideum, that serves as an excellent model system for investigating the molecular mechanisms that underlie cell motility. Dictyostelium amoeba crawl over surfaces, extend and retract protrusions, change shape, engulf other microorganisms and divide by splitting into two. All of these types of movement depend on the interaction of a myosin motor protein with a network of filaments made up of the protein actin. Myosins have the unique ability to convert chemical energy into movement along actin filaments. Most cells contain several different types of myosin, all of which consist of a large subunit, or heavy chain, that is bound to one or more smaller subunits, or more light chains. The light chains play a critical role in regulating the activity of myosin, but surprisingly, for most myosins the identity of the light chain subunits remain unknown. Over the last several years we have made considerable progress in identifying the light chain subunits of the Dictyostelium myosins. Unexpectedly, we have discovered that most Dictyostelium myosins have unique light chains. We have also discovered another mechanism that regulates myosin, which involves a protein kinase, termed PakB, that can attach a phosphate to the heavy chain of the myosin. In the proposed research we will examine how the myosin heavy chains and light chains recognize each other and how the choice of the light chain effects the function of myosin in the cell. We also will carry out studies to better understand the regulation of PakB. Together, these studies will provide important new insights into the regulation of myosin motor proteins in cells. Over the last five years three MSc students and three PhD students have been trained on this project. New students trained on this project will gain experience in a range of techniques, including molecular biology, protein biochemistry, structural analysis and cell biology, that are in demand by academic researchers and by biotechnology and pharmaceutical industries.