Striated muscle functions universally to generate biological force. We will study assembly and function if striated muscle. Our approach is largely genetic and uses the nematode Caenorhabditis elegans as a model organism. Genetic techniques are complementary to biochemical techniques for the study of muscle. Mutations that cause muscle dysfunction define genes required to construct a normal muscle cell. The nature of mutant defects provides insights into functions of the wild-type proteins. We will use genetics to investigate the structure and assembly o( nematode muscle. Mutants that are affected in the protein components of muscle will be identified and analyzed using a combination of genetic, molecular, and ultrastructural techniques. We will investigate the in vivo functions of myosin light chain proteins by identifying mutants that result from myosin light chain defects. Genes that are functionally related to myosin light chains will also be studied. We will investigate the assembly of thick myofilaments by characterizing mutations of a myosin heavy chain gene that interfere with assembly. We will identify specific amino acid residues of the myosin heavy chain molecule that are important for thick filament assembly. Thick filament proteins with which myosin interacts during assembly will be identified. Our long range goals are to determine how many genes are required for muscle assembly and function, to describe the protein products of those genes, and to understand how those proteins function during muscle assembly and contraction. This work is significant for understanding the genetic origins of human muscular disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030132-11
Application #
3277740
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1982-02-01
Project End
1994-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Rushforth, A M; White, C C; Anderson, P (1998) Functions of the Caenorhabditis elegans regulatory myosin light chain genes mlc-1 and mlc-2. Genetics 150:1067-77
Maryon, E B; Saari, B; Anderson, P (1998) Muscle-specific functions of ryanodine receptor channels in Caenorhabditis elegans. J Cell Sci 111 ( Pt 19):2885-95
Rushforth, A M; Anderson, P (1996) Splicing removes the Caenorhabditis elegans transposon Tc1 from most mutant pre-mRNAs. Mol Cell Biol 16:422-9
Maryon, E B; Coronado, R; Anderson, P (1996) unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction. J Cell Biol 134:885-93
Rushforth, A M; Saari, B; Anderson, P (1993) Site-selected insertion of the transposon Tc1 into a Caenorhabditis elegans myosin light chain gene. Mol Cell Biol 13:902-10
Kim, Y K; Valdivia, H H; Maryon, E B et al. (1992) High molecular weight proteins in the nematode C. elegans bind [3H]ryanodine and form a large conductance channel. Biophys J 63:1379-84
Bejsovec, A; Anderson, P (1990) Functions of the myosin ATP and actin binding sites are required for C. elegans thick filament assembly. Cell 60:133-40
Collins, J; Forbes, E; Anderson, P (1989) The Tc3 family of transposable genetic elements in Caenorhabditis elegans. Genetics 121:47-55
Pulak, R A; Anderson, P (1988) Structures of spontaneous deletions in Caenorhabditis elegans. Mol Cell Biol 8:3748-54
Bejsovec, A; Anderson, P (1988) Myosin heavy-chain mutations that disrupt Caenorhabditis elegans thick filament assembly. Genes Dev 2:1307-17

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