The PDZ protein discs-large (DLG): The 'Jekyll and Hyde' of the epithelial polarity proteins

Abstract

Discs-large (DLG) is a multi-PDZ domain-containing protein that belongs to the family of molecular scaffolding proteins known as membrane guanylate kinases or MAGUKs. DLG is a component of the Scribble polarity complex and genetic analyses of DLG in Drosophila have identified a role for the protein in several key biological processes including the regulation of apico-basal polarity of epithelial cells, as well as other polarity processes such as asymmetric cell division and cell invasion. Disturbance of DLG function leads to uncontrolled epithelial cell proliferation and neoplastic transformation, thereby defining DLG as a potential tumour suppressor. However, whether mammalian homologues of DLG (DLG1, DLG2, DLG3 and DLG4) also possess tumour suppressor functions is not known. In this minireview, we focus on the biological functions of DLG1 in human epithelial cells and on how the function of this MAGUK relates to its intracellular location. We examine some of the evidence that implies that DLG has both tumour suppressor and, paradoxically, oncogenic functions depending upon the precise cellular context. A systematic study of the chemical characteristics needed for antibody binding to the cruzipain sulfated epitope was performed by immunoassays. Different molecules were synthesized, coupled to BSA/aprotinin, and confronted with rabbit/mice sera specific for Cz/C-T and purified IgGs from immune and human Chagas disease sera, demonstrating that synthetic GlcNAc6S mimics the N-glycan-linked-sulfated epitope displayed in the C-T domain of natural cruzipain © 2012 The Authors Journal compilation © 2012 FEBS.