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Joseph W. Sanger,

Joseph W. Sanger

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Emeritus Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology

Contact information
Laboratory for Cell Motility Studies
Room1014 BRB II/III.
Department of Cell and Developmental Biology
University of Pennsylvania
School of Medicine
421 Curie Boulevard
Philadelphia, PA 19104-6058
Office: 215 898-6919
Fax: 215 898-9871
Education:
B.S. (Major: Biology, Minor: Chemistry; with honors)
Manhattan College, New York, NY, 1962.
Ph.D.
Dartmouth University, 1968.
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Description of Research Expertise

RESEARCH INTERESTS

Cellular analysis of the formation of myofibrils, stress fibers, and cleavage furrows in living cells, and mechanisms of movement of the infectious bacterium listeria monocytogenes.

DESCRIPTION OF RESEARCH

The heart is the first organ to differentiate and function in the embryo. Cardiac muscle cells synthesize sarcomeric proteins, which assemble into myofibrils. These early myofibrils are responsible for the first contractions and, later, for the continuous contractions of the growing heart with full capability of undergoing mitosis and cytokinesis. Upon cell division, myofibrils can disassemble into their component filaments and molecules, some of which are used to form the contractile cleavage furrow used in cytokinesis. The precise developmental cascade of myfibrillogenesis in both cardiac and skeletal muscle cells is poorly understood.

As the spreading edges of the cell surface advance, the previously formed premyofibrils are left in place, which would permit other large proteins (e.g., muscle myosin II and titin) to gain access to the minisarcomeres. Premyofibrils are not, as some have suggested, breakdown products of mature myofibrils. The Z-bodies of the premyofibrils appear to fuse laterally with one another to form the Z-bands of mature myofibrils, and with increasing time, mature myofibrils and Z-bands emerge in regions where linear arrays of Z-bodies had been. A proposed three stage model of myofibril formation progresses with premyofibrils to nascent myofibrils to mature myofibrils.

Premyofibrils, found at the spreading edges of the cardiomyocytes, are composed of minisarcomeres. The sarcomeric equivalent of the Z-band in the premyofibril is a Z-body; both contain the cytoskeletal protein alpha actinin. This protein is found concentrated in stress fibers, Z-bodies and Z-bands of muscles marking the boundaries of the sarcomeric units in nonmuscle stress fibers and in muscle myofibrils. Our results have demonstrated premyofibrils precede in space and time to mature myofibrils. These beaded Z-bodies are attached to the cell surface and are responsible for the attachment of the short actin filaments to the cell surfaces. Most importantly, premyofibrils contain nonmuscle myosin IIB, which is believed to be responsible for the antipolar arrangement of the actin filaments in these minisarcomeres.

Selected Publications

Sanger, J. W., J. M. Sanger and C. Franzini-Armstrong: Assembly of the skeletal muscle cell. Myology, 3rd Edition. A. G. Engel and C. Franzini-Armstrong (eds.). McGraw-Hill, New York, In Press.

Malish, H. R. N. L. Freeman, D. V. Zurawski, P. Chowrashi, J. C. Ayoob, , J. W. Sanger, and J. M. Sanger: Potential Role of the EPEC Translocated Intimin Receptor (Tir) in Host Apoptotic Events. Apoptosis 8: 179-90, Mar 2003.

Du A, Sanger JM, Linask KK, Sanger JW. : Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm. Dev Biol. 257(2): 382-94, May 15 2003.

Huang, L., Mittal, B., Sanger, J. W. and Sanger, J. M.: Host focal adhesion protein domains that bind to the translocated intimin receptor (Tir) of Enteropathogenic Escherichia coli (EPEC). Cell Motil. Cytoskeleton 52: 255-265, 2002.

Zajdel, R. W., J. M. Sanger, C. R. Denz, S. Lee, S. Dube, J. W. Sanger and D. K. Dube: A novel striated tropomyosin incorporated into organized myofibrils of cardiomyocytes in cell and organ cultures. FEBS Lett. 520: 35-39, 2002.

Chowrashi, P., B. Mittal, J. M. Sanger and Joseph W. Sanger: Amorphin is phosphorylase; phosphorylase is an alpha-actinin-binding protein. Cell Motil. Cytoskeleton 53: 125-135, 2002.

Sanger, J. W., P. Chowrashi, N. C.Shaner , S. Spalthoff , J. Wang , N. Freeman , and J. M. Sanger: Myofibrillogenesis in skeletal muscle cells. Clin Ortho Related Res 403S: S153-S162, 2002.

Shaner, N. C., J. W. Sanger and J. M. Sanger: Lowering of cellular ATP levels inhibits actin depolymerization in EPEC/EHEC pedestals and Listeria tails. Mol. Biol. Cell 13: 177a, 2002.

Wang, J., B. Mittal, M. Lee, J. M. Sanger and J. W. Sanger: Spatial, temporal and dynamic studies of Z-band proteins in live muscle cells. Mol. Biol. Cell 13: 459a, 2002.

Du, A., J. M. Sanger and J. W. Sanger: Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm. Mol. Biol. Cell 13: 459a, 2002.

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Last updated: 08/30/2004
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