The Role of Drosophila Merlin in the Control of Mitosis Exit and Development
Annual rept. 1 Jul 2005-30 Jun 2006
CHILDRENS RESEARCH INST COLUMBUS OH
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Presently the mechanism by which Merlin functions as a tumor suppressor is not understood. By utilizing Drosophila genetics, we have found a role of Merlin in the control of mitosis exit. Merlin mutations lead to two types of mitosis exit asynchrony the asynchronous anaphase-telophase figures and the asynchronous telophase-interphase figures. Also we show that cells lacking Merlin possess greater ability to overcome vein restriction in the wing. The Merlin protein is colocalized with the Wingless morphogen in the cells at the dorsaliventral compartment border of the wing imaginal disc. Merlin inactivation may lead to an alteration on the determinationmaintenance of Wg stripe expression. We have found potential genetic interactions between the Merlin and porcupine genes and between the Merlin and shibire genes. We also discover an interaction between the Merlin and lap like-Ap180 which is important for clathrin-mediated endocytosis of synaptic vesicles was identified. Our results suggest that Merlin counteracts with Lap and through Lap Merlin may regulate the EGFR pathway required for vein fate determination in the wing. In addition by analyzing the evolution diversity and overall distribution of Merlin among different taxa we demonstrate a monophyletic origin of the Merlin proteins with their root in the early metazoa. The overall similarity among the primary and secondary structures of all Merlin proteins and the conservation of several functionally important residues suggest a universal role for Merlin in a wide range of metazoa.
- Medicine and Medical Research