Since myosin is the source of force generation in muscle, an understanding of myosin function is essential to progress in the analysis and treatment of muscular defects. At present, however, the basic model of myosin function, the swinging cross-bridge model, remains unproven. Furthermore, while regions of the myosin molecule involved in ATP and actin binding have been identified, the roles of several highly conserved domains of the myosin molecule remain obscure. Cold-arrested myosin mutants represent tools for observing previously inaccessible aspects of myosin function, and most of the mutants to be studied lie in a region of unknown function. The mutants will be characterized in terms of 1) sequence changes leading to cold sensitivity, 2) ability to interact with actin during cold arrest, 3) point in the ATPase cycle at which they are blocked, and 4) morphology of cold-arrested actomyosin complexes. By determining the point in the ATPase cycle at which the mutants arrest, and the morphology of the actomyosin complexes at these points, the role of the highly conserved region can be determined and key postulates of the swinging cross-bridge model and be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AR008235-01
Application #
3032093
Study Section
Physiological Sciences Study Section (PSF)
Project Start
1992-12-31
Project End
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Patterson, B; Spudich, J A (1995) A novel positive selection for identifying cold-sensitive myosin II mutants in Dictyostelium. Genetics 140:505-15
Springer, M L; Patterson, B; Spudich, J A (1994) Stage-specific requirement for myosin II during Dictyostelium development. Development 120:2651-60