A novel Dlg isoform and identification of its interacting proteins

描述（申请人提供）：黑腹果蝇是研究动物发育和癌症形成的优秀模式生物，因为涉及的关键蛋白质在所有动物中都是保守的，而苍蝇提供了巨大的实验优势。disc - large （Dlg）蛋白家族最初在果蝇中被鉴定为肿瘤抑制因子，随后在哺乳动物中鉴定出多个Dlg同源物。目前已知它们在果蝇中建立顶-基底细胞极性、形成细胞-细胞接触以及在细胞膜细胞质面组装大蛋白复合物方面发挥着关键作用。在哺乳动物中，Dlg同源物hDlg的截断会导致颅面畸形和围产期死亡。然而，Dlg的潜在机制在很大程度上仍然是未知的。

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.