    |
||
|
|
xxx |
Carole L. Moncman Striated
muscles are responsible for a majority of the motile events in large
multi-cellular organisms. Cardiac
muscle is responsible for pumping blood throughout an entire organism and is
capable of sustaining continuous contractile activity for over 100 years.
Skeletal muscles are responsible for all voluntary movements.
While these two muscle types differ in their functions, both muscle types
achieve their goals via the same functional unit: the striated myofibrils.
The striated myofibrils are a highly ordered array of numerous
filamentous networks that contain 100's of proteins. Several
decades of muscle research have led to the identification of major myofibrillar
proteins and have even elucidated the mechanisms responsible for the production
of force and contractile activity in these tissues.. The genetic basis for
muscular disorders, such as familial hypertrophic cardiomyopathy, muscular
dystrophy, and nemaline myopathy , have
also been identified. Minor changes
in the primary structure or targeting signals of a single protein component of
the striated myofibrils can have dramatic effects on the organization and
function of the entire tissue. Yet
with all this research, little is known about the course of events responsible
for the formation of this near crystalline lattice found in the striated
myofibrils. A major goal of our research is to elucidate the mechanisms involved in myofibril assembly. To this end, we have a identified a novel member of the nebulin family of actin binding proteins that is found exclusively in cardiac muscle, nebulette. We have determined the temporal pattern of expression of this protein and have characterized its complete cDNA. Using the jellyfish green fluorescent protein as a tag, we have expressed truncated forms of nebulette in cardiomyocytes and have assessed the role of the different domains of this protein in the assembly and function of the cardiac myofibrils. Our current research efforts are geared toward fully characterizing the molecular interactions of nebulette by the identifying binding partners using the yeast two hybrid system and complete analysis of known interactions. This work will involve the use of molecular genetic techniques for expression of proteins in both prokayrotic and eukaryotic systems, as well as, biochemical and biophysical techniques to assess the molecular interactions.
Moncman, C. L. and
F. H. Andrade. 2007. Nebulin isoforms in the Extraocular Muscle. Cell
and Tissue Research. Feb;327(2):415-20. Epub 2006 Oct 12. Moncman,
C. L. and K. Wang. 1995. Nebulette:
A 107 kD nebulin-like protein in cardiac muscle.
Cell Motil. Cytoskel. 32:
205-225. Moncman,
C. L. and K. Wang. 1996. Assembly
of nebulin into the sarcomeres of avian skeletal muscle.
Cell Motil. Cytoskel. 34:
167-184. Kinose, F., S. X. Wang, U. S. Kidambi, C. L. Moncman, and D. A. Winkelmann. 1996. Glycine 699 is pivotal for the motor activity of skeletal muscle myosin. J. Cell Biol. 134: 895-909. Moncman,
C. L., and K. Wang. 1998. Effects of
thiol protease inhibitors on myoblast fusion and myofibril assembly.
Cell Motil. Cytoskel. 40:
354-367. Moncman,
C. L., and K. Wang. 1999. Functional
dissection of nebulette demonstrates actin binding of nebulin-like repeats and
Z-line targeting of SH3 and linker domains.
Cell Motil. Cytoskel. 44:1-22. Moncman, C. L. and K. Wang. 2000. Architecture of the thin filament Z-line junction: Lessons from protein homologies. J. Mus Res. Cell Mot. |
