Research Interests:

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.

REPRESENTATIVE PUBLICATIONS

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.

Panaviene,  Z., and C. L. Moncman. 2007. The linker region of nebulin family members plays an important role in targeting these molecules to cellular structures.  Cell and Tissue Research. Feb;327(2):353-69. Epub 2006 Oct 3.

Esham, M., K. Bryan, J. Milnes, W. B. Holmes and C. L. Moncman.  2007. Developmental Analysis of Nebulette Expression During Early Stages of Cardiogenesis. Cell Motil Cytoskeleton. 2007 Jan 19; [Epub ahead of print]

Panaviene, Z., X. A. Deng, M. Esham and C.L. Moncman. 2007. Targeting of nebulin fragments to the cardiac sarcomere. Exp Cell Res. March; 313(5):896-909 Epub 2006 Dec 30.

Senetar, M., C.L. Moncman and R. O. McCann. 2007.  Talin2 is induced during muscle differentiation and is targeted to stable adhesion complexes. Cell Motil Cytoskeleton. 2007 Mar;64(3):157-73. Epub 2006 Dec. 20

Schowalter, Rachel M., Mark A. Wurth, Carole L. Moncman, Richard O. McCann and Rebecca Ellis Dutch. 2006.  Rho GTPase activity modulates paramxyovirus fusion protein function. Virology 350(2):323-34.

Wang, Q., C. L. Moncman and D. A. Winkelmann 2003.  Mutations in the Motor
Domain Modulate Myosin Activity  and Myofibril Organization. J Cell Science.
116:4227-4238.

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.