Drosophila melanogaster Guk-holder interacts with the Scribbled PDZ1 domain and regulates epithelial development with Scribbled and Discs Large

摘要: Epithelial cell polarity is controlled by components of the Scribble module, and its regulation critical for tissue architecture proliferation migration. In Drosophila melanogaster, adaptor protein Guk-holder (Gukh) binds to Scribbled (Scrib) Discs Large (Dlg) module plays an important role in formation neuromuscular junctions. However, Gukh's epithelial molecular basis Scrib-Gukh interaction remain be defined. We now show using isothermal titration calorimetry that Scrib PDZ1 domain major site with Gukh. Furthermore, we defined structural this determining crystal structure PDZ1-Gukh complex. The C-terminal PDZ-binding motif Gukh located canonical ligand-binding groove utilizes unusually extensive network hydrogen bonds ionic interactions enable binding high affinity. next examined along those Dlg tissues found expressed larval-wing eye-epithelial co-localizes at apical cortex. Importantly, functions development tissues, depletion enhancing eye- wing-tissue defects caused or depletion. Overall, our findings reveal Scrib's has a key Drosophila.