The Functional Study Of Tankyrase In Drosophila Growth And Development

Tankyrases (TRF1-interacting ankyrin related ADP-ribose polymerase) are protein members of the poly (ADP-ribose) polymerase family bearing several ankyrin repeats domains, a SAM domain and a PARP domain, regulating the length of human telomere. They play an important role in telomere maintenance, and are associated with the sister chromatid separation and glucose uptake. Recent research has indicates that tankyrases are also involved in the Wnt signaling. In mouse, neither tankyrasel nor tankyrase2deficiency mice has any observable on telomere length maintenance. However, double knockout of tankyrasel and tankyrase2causes mouse embryonic lethality, suggesting functional redundancy of the two genes. Despite of their important roles in mouse and human, little is known about the function of tankyrase in Drosophila development. In this study, Drosophila was used as a model to examine the function of tankyrase through genetic methods. The mutant flies of tankyrase were generated through the P element-mediated knockout technique. The mutant strain was used to systematically assess possible functions of tankyrase in Drosophila. Animal lacking the activity of tankyrase appear of viable. However, some defects in metabolism and development were observed on the mutant flies These defects include low egg hatchability, high glucose concentration, low TAG concentration and decreased tolerance of starvation. These data suggest that tankyrase is involved in the regulation of energy metabolism.We also examined the function of tankyrase by overexpression approach. Overexpression of tankyrase in whole body caused lethality in larvae stage. Overexpression of tankyranse in tissues resulted in tissue damage. The TLTNEL analysis revealed that tankyrase can induce cell apoptosis in wing imagnal discs and this phenomenon can be rescued by co-expression of the Baculoviru protein p35. Nevertheless, in adult eye and wing, co-expression of p35with tankyrase only slightly blocked the defects, indicating that overexpression of tankyrase may produce other effects besides cell apoptosis. We further showed that the ankyrin-repeats domain, but not the PARP domain of tankyrase, played a unique role in fly development.