DLG PROTEIN IS REQUIRED FOR JUNCTION STRUCTURE, CELL POLARITY, AND PROLIFERATION CONTROL IN DROSOPHILA EPITHELIA

The Discs large (Dig) protein of Drosophila is the prototypic member o f a growing family of proteins termed membrane-associated guanylate ki nase homologs (MAGUKs), The MAGUKs are composed of a series of peptide domains that include one or three DHR/PDZs an SH3 and a region homolo gous to guannylate kinase (GUK). We have previously shown that the pro duct of this gene, the Dig protein, is localized at the septate juncti ons between epithelial cells, and that mutations in the gene cause neo plastic overgrowth of thr imaginal discs. The dlg locus is therefore d efined as a tumor suppressor gene. In this paper, we show that the Dig protein is localized on the cytoplasmic face of the septate junction and is required for the maintenance of this structure. It is also requ ired for proper organization of the cytoskeleton, for the differential localization of membrane proteins, and for apicobasal polarity of epi thelial cells, However, these other functions can be uncoupled from Di g's role as a tumor suppressor since mutations in two domains of the p rotein, the SH3 and GUK, cause loss of normal cell proliferation contr ol without affecting the other functions of the protein. These results suggest that, besides regulating cellular proliferation, the Dig prot ein is a critical component of the septate junctions and is required f or maintaining apicobasal polarity in Drosophila epithelium.