Download Drosophila melanogaster

Localization of cMyBP-C in transgenic Drosophila melanogaster flight muscle
Cardiac myosin-binding protein C (cMyBP-C) is a thick filament protein that is
critical for proper cardiac muscle function. cMyBP-C increases the stiffness of the
thick filaments and aids in their assembly during development. In humans,
mutations in cMyBP-C can lead to familial hypertrophic cardiomyopathy. In
Drosophila melanogaster, another myosin-binding protein called flightin is
expressed in the indirect flight muscle (IFM) and performs some functions
analogous to those of cMyBP-C with respect to the thick filaments. Specifically,
IFM thick filaments devoid of flightin are longer and more compliant than thick
filaments containing flightin, indicating that flightin influences IFM thick filament
assembly and stiffness. Moreover, evidence suggests that flightin and cMyBP-C
bind to a common region in myosin. The two myosin-binding proteins are
structurally very different and are taxonomically unrelated, but their similar
effects and potential common myosin binding site in the different muscles in
which they are expressed might signal their functional homology. Previous work
in the Vigoreaux lab developed a series of transgenic D. melanogaster expressing
cMyBP-C in the IFM to test this idea. Flight was not rescued in flies expressing
cMyBP-C in a flightin null background, but sarcomere length differed from that of
the flightin null. The stiffness of the thick filament was shown to be greater in a
flightin/cMyBP-C coexpression line than in the flightin rescue control. To better
interpret these results and understand the effects cMyBP-C has when expressed
in IFM, its sarcomeric distribution was examined using immunohistochemistry.
Preliminary results indicate that the presence of flightin influences the sarcomeric
distribution of cMyBP-C in the IFM. These studies are being expanded to
determine if competition for binding to a common myosin site can explain the
sarcomeric distribution of cMyBP-C in the presence and absence of flightin.