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.