Movement of and within cells is fundamental to life, whether in development of an organism, defense against infection, repair after injury, or in pathologies such as cancer and heart disease. Myosin was first identified in skeletal muscle as a motor protein critical to muscle contraction. Two heavy and two pairs of light chains comprise this conventional myosin (now known as myosin II), which polymerizes into filaments to interact with actin and generate force through the hydrolysis of ATP. Dr. Korn has been studying the function and regulation of the actomyosin system in its diverse forms since he discovered the first unconventional non-filamentous myosin, myosin I (containing only a single heavy chain), in the single-cell soil protozoan Acanthamoeba castellanii, approximately forty years ago.
Genomic approaches currently divide the myosin superfamily into 35 classes with many thousands of members. Multiple myosins are found in single eukaryotic cells and have very specific roles in distinct cellular processes including cell division, chemotaxis, and translocation of organelles. Each of these functions exists under tight regulatory control. Dr. Korn’s laboratory brings the tools of biochemistry and cell biology to focus on three research areas: the role of the actin cytoskeleton in Dictyostelium fruiting body development, the molecular basis of the regulation of actin-activated ATPase activity in myosin II, and the mechanism of association of myosin I with cell membranes.
Dictyostelium amoebae have long been a model system for studying cellular functions. Starvation induces these cells to secrete cAMP, which attracts other cells to spur the formation of multicellular mounds that differentiate and develop into fruiting bodies containing spores of Dictyostelium. Recently, Dr. Korn and his colleagues have found that these sequential processes of cAMP signaling, chemotaxis, development, and differentiation are dependent on the integrity of the actin cytoskeleton. They are partially or completely aborted by mutations of a specific tyrosine residue in actin, and by deletion of actin crosslinking proteins cortexillin I and II, both of which affect actin filament assembly.
The assembly and enzymatic activity of some myosins is regulated by phosphorylation of their heavy chains. Dr. Korn has recently found that the actin-activated ATPase activity of Acanthamoeba myosin II is down-regulated by phosphorylation of a serine in loop-2 of the motor domain, a region known to be at the actin-myosin interface, and that filament formation of Acanthamoebamyosin II is regulated by phosphorylation of up to four serines in a repeating sequence in the non-helical tailpiece of its two heavy chains.
To influence cell shape and motility, as well as intracellular transport, the actomyosin system interacts with cell membranes. Dr. Korn’s laboratory is interested in the mechanism of association of class I myosins with membranes, in particular the basis of the association of different class I myosins with different membranes in the same cell. He and his colleagues have now extended initial studies that identified a basic-hydrophobic region responsible for the co-localization of Acanthamoeba myosin IC and Dictyosteliummyosin IB with phosphatidylinositol 4,5-bisphosphate in the plasma membrane.
Through these discrete yet interconnected research paths, the Korn lab hopes to better characterize the diverse functions of the actomyosin system at the molecular level and improve our understanding of this important cellular system.