Molecular mechanisms of intracellular motility

Telephone: (301) 496-6887

E-mail: sellersj@nhlbi.nih.gov

Office: Building 10, Room 8N117

Mailing Address:
National Heart, Lung, and Blood Institute (NHLBI)
10 Center Drive, MSC 1762 

Bethesda, Maryland 20892-1762 

• Motility Assay 
• Myosin Phylogenetic Tree 
• Myosin Function Domains 

Our research focuses on the structure, function and regulation of myosin, the actin-dependent motor protein. While much of our work has been performed on smooth and nonmuscle myosin II isoforms, we have a growing interest in the unconventional myosin classes. The tails of each class of myosin have distinct features that may include many possible functional motifs. Myosins from class I, II, V, VI, VII, IX, X and XV have been identified in mammals. Human diseases have been associated with mutations in several myosin genes, including the beta-cardiac myosin heavy chain and light chains (hypertrophic cardiomyopathy), the myosin VA heavy chain (Griscelli's syndrome), the myosin VIIA heavy chain (Usher's IB syndrome), and the myosin XV heavy chain (DFNB3). The latter two diseases are deafnesses. Many of the myosin classes are represented by multiple genes within a given organism. In addition to numerous muscle specific myosin heavy chain genes, there are at least eighteen myosin genes that may be expressed in mammalian nonmuscle cells, including 7 genes for myosin I alone. We are very interested in the specific roles and functions of this variety of myosins. We are studying myosins from class I, II, III, V, X, and XV. The techniques that are used range from transient kinetic studies of isolated myosins to genetic analysis of myosin function in Drosophila. We routinely utilize the actin sliding in vitro motility assay and steady state enzymatic analysis to characterize myosins. We are making extensive use of baculoviral expression of myosin in Sf9 cells in order to prepare naturally occurring isoforms of myosin as well as mutant myosins. For these studies we use the available three dimensional structures of various myosin head fragments as a guide.