This proposal addresses the important general biological problem of the mechanisms of regulated assembly of precisely organized intracellular structures and more specifically the problem of how the thick filaments form within sarcomeres of skeletal muscle. The goal of the proposal is to test the hypothesis that self-assembly of contractile proteins is guided by additional sarcomere proteins. This is a hypothesis driven proposal that emerges from a long term set of investigations by this investigator into thick filament assembly in C. elegans. The approach is to exploit the investigator's recent findings of additional proteins associated with the principal thick filament proteins, myosin A, B, C, D and paramyosin. He postulates that these associate proteins facilitate assembly and that one group is a structural component of thick filaments. These additional proteins are designated as myosin assemblase which act catalytically and rod coupling proteins which act stoichiometrically in directing assembly providing rigidity to the filaments. The former is the product of the Unc-45 gene and the latter are a family of proteins designated filagenins, a, b and g. Using a variety of genetic, molecular genetic, immunological, biochemical, and imaging approaches the PI will use the nematod model system to demonstrate the correctness of his hypothesis and extend the observations into Drosophila and mice to demonstrate common mechanistic themes across phyla.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055623-04
Application #
6386674
Study Section
Special Emphasis Panel (ZRG2-CBY-1 (01))
Program Officer
Deatherage, James F
Project Start
1998-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2003-07-31
Support Year
4
Fiscal Year
2001
Total Cost
$241,096
Indirect Cost
Name
Baylor College of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030