A novel Dlg isoform and identification of its interacting proteins

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DESCRIPTION (provided by applicant): Drosophila melanogaster is an excellent model organism to study animal development as well as formation of cancer because the critical proteins involved are conserved in all animals, and flies offer tremendous experimental advantages. The Discs-Large (Dlg) family of proteins was originally identified as a tumor suppressor in flies, and multiple mammalian Dlg homologs were subsequently identified. They are now known to play critical roles in establishing apical-basal cell polarity, formation of cell-cell contacts, and assembly of large protein complexes on the cytoplasmic faces of membranes in flies. In mammals, truncation in one of Dlg homologs, hDlg, results in craniofacial dysmorphogenesis and perinatal death. However, the underlying mechanism of Dlg is still largely unknown. Completion of fly genome sequence and the recovery of many new dlg cDNAs recently revealed the presence of multiple Dlg isoforms that were previously unnoticed. The principal investigator discovered that one of those multiple Dlg isoforms, Dlg-75, may carry out many of Dlg functions previously assigned to the prototype Dlg-A. To understand the function of Dlg-75, she will search for the interacting proteins of Dlg-75 using two approaches. First, a set of powerful genetic screens will be carried out to select for the genes modulating the activity or level of Dlg-75. Second, proteins that are capable of physically interacting with Dlg-75 will be identified with two-hybrid screen. Both screens are simple and effective and take relatively short time to carry out. Considering that Strabismus (Stbm), a Dlg-75-interacting protein, is essential for neural tube formation of mice, identification of Dlg-75-interacting proteins from these screens will greatly facilitate understanding on the mechanism of Dlg and Stbm in growth control, cell polarity, and development in both flies and humans.