The goal of this application is to use the approach of molecular genetics to understand the interactions between protein components of myofibrils as they relate to function. Specifically, the intent is to understand the interactions between the myosin heavy chain and myosin light chains as they relate to the activity of the myosin linked ATPase. Drosophila will be used as a model system for looking at the interaction of myofibrillar proteins. Initially it will be established that the myosin light chain-1 protein is required for normal indirect flight muscle activity. Then, the hypothesis that the """"""""EF hand"""""""" domain of the myosin light chain-1 protein is required for the activity of the myosin linked ATPase will be tested. This hypothesis can be tested in Drosophila because of the recent technological advance in P-mediated transformation of Drosophila eggs with cloned DNA. Using brute force Drosophila genetics a null allele of the myosin light chain-1 will be isolated. This null mutant will provide the correct genetic background for transformation experiements in which in vitro mutagenized myosin light chain-1 DNA is introduced via P-mediated transformation. The activity of the myosin linked ATPase will be assayed in the transformants which contain the altered Ca++ binding domain. The success of this molecular genetic approach using a major structural protein will allow future studies to be initiated that are focused upon minor myofibrillar proteins (whose functions are unknown at present) which may be involved in the assembly or activity of this macromolecular structure.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033270-02
Application #
3282743
Study Section
Genetics Study Section (GEN)
Project Start
1984-06-01
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210