Carol Gregorio
Associate Professor of Cell Biology and Anatomy
Ph. D., Roswell Park Cancer Institute, Buffalo, New York
Postdoctoral Research, The Scripps Research Institute, La Jolla, California
Teaching Areas- Graduate Cell Biology
E-mail: gregorio@email.arizona.edu
Research Interest:
Identification of the molecular components and signaling mechanisms that regulate cytoskeletal protein interactions during striated muscle development.
The research in my laboratory is focused on identifying the components and molecular mechanisms regulating actin filament length, assembly and organization. Control of actin filament length and dynamics is important for cell motility and architecture and is regulated in part by capping proteins that block elongation and depolymerization at both the fast-growing (barbed) and slow-growing (pointed) ends. To identify the role of various actin-binding proteins, including tropomodulin, the only recognized actin filament pointed end capping protein, primary cultures of chick cardiac myocytes and skeletal myogenic cells are being used as model systems. Striated muscle is an ideal model system for these studies due to the precise organization and polarity of cytoskeletal components within repeating sarcomeric units (for example, the ~1 mm long actin filaments are easily resolved by light microscopy). Using this system we can combine morphological and biochemical approaches with direct tests of physiological function.
Recently, we demonstrated that pointed end capping by tropomodulin is required to maintain actin filament length in vivo and that this is essential for contractile function. In addition, our results indicate that separate domains of tropomodulin subserve different physiological properties. We are presently using two approaches to identify further the in vivo functional properties of tropomodulin. These include: 1) microinjection of domain-specific, function-blocking antibodies and 2) overexpression of truncated or mutant tropomodulins by cDNA transfection or by microinjection of recombinant tropomodulin fragments.
In the future, to complement the studies described above, the role of tropomodulin and other actin regulatory proteins will be studied in motile cells: that is, in cells where actin filament lengths are maintained at different lengths.
Selected Publications:
McElhinny, A.S., C.N. Perry, C. Witt, S. Labeit and C. C. Gregorio. (2004) Muscle specific RING finger-2 (MURF-2) has multiple subcellular localizations and is required for microtubule, intermediate filament, and sarcomeric M-line maintenance in striated muscle. J. Cell Science, 117:3175-88.
McElhinny, A., Kakinuma, K., Sorimachi, H., Labeit, S. and C.C. Gregorio. (2002) Dual roles of MURF-1 in the regulation of sarcomeric M-line structure and in the potential modulation of gene expression via its interaction with titin and GMEB-1. J. Cell Biology, 157:125-36.
Kazmierski, S.T., Antin P.B., Witt, C., McElhinny, A.S., Labeit, S. and C.C. Gregorio. (2003) The Complete Mouse Nebulin Gene Sequence and the Expression of Cardiac Nebulin. J. Molecular Biology, 328:835-46.
Mudry, RE, Perry, CN, Fowler V.M., and C.C. Gregorio. (2003) The Interaction of Tropomodulin with Tropomyosin Stabilizes Thin Filaments in Cardiac Myocyte. J. Cell Biology, 162: 1057-68.
Clark K., McElhinny A.S., Beckerle M. and C.C Gregorio. (2002) Striated muscle cytoarchitecture: an intricate web of form and function. Ann. Rev. Cell Dev. Biol. 18:637-706.
Bang, M.L., Mudry, R.E., McElhinny, A.S., Trombitas, K., Geach, A.J., Yamasaki, R., Sorimachi, Granzier, H., Gregorio, C.C., and S. Labeit. (2001) Myopalladin, a novel 145 kDa sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. J. Cell Biology, 153:413:28.
Gregorio, C.C. and P.B. Antin, (2000) At the heart of myofibril assembly. Trends in Cell Biology, 10:355-362.
McElhinny, A.S., Kolmerer, B., Fowler, V.M., Labeit, S. and C.C. Gregorio. (2000) The N-terminal end of nebulin interacts with tropomodulin at the pointed ends of the thin filaments. J Biological Chemistry 276:583-592.
Gregorio, C.C., A. Weber, M. Bondad, C.R. Pennise and V.M. Fowler (1995) Requirement of pointed end capping by tropomodulin to maintain actin filament length in embryonic chick cardiac myocytes. Nature 377:83-86.
