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In striated muscle, the barbed ends of thin filaments are attached to Z
lines. To mediate this attachment, biochemical and cell biological studies
suggest that actin capping protein (CP) binds the barbed ends of actin filaments
and alpha-actinin crosslinks overlapping filaments from adjacent sarcomeres. My
previous studies in transgenic mouse hearts support the hypothesis that CP
attaches actin filaments to the Z line. Defective interaction between CP and the
actin thin filaments causes major structural defects in sarcomere organization
and leads to cardiac hypertrophy and lethality. The goal of my research is to
understand how thin filaments are attached to Z-lines and how defects in this
attachment can affect the structure and function of the heart. In my lab, we are
characterizing an existing mouse model for human cardiomyopathy which is caused
by a defect in a sarcomere component. In addition, we are identifying
interacting proteins of the Z-line, and defining the function of the CP alpha
subunit in the heart. Techniques employed include immunolocalization, Northern
blot analysis, Western blot analysis, light microscopy, fluorescent microscopy,
transmission electron microscopy, cardiac catherization, ECG, GST pulldown
analysis, co-immunoiprecipitation, and yeast two hybrid analysis.
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