The role of PATJ in the development of Drosophila melanogaster

In the due course of the formation of apical-basal polarity the transmembrane protein Crumbs (Crb) and its intracellular adaptor protein Pals1 (Protein associated with Lin seven 1, Stardust, Sdt in Drosophila) have been found to play key roles in the establishment and maintenance of cell polarity in various types of tissues. Research in Drosophila revealed that PATJ (Pals1 associated tight junction protein) which have been reported to be a part of the trimeric complex with Crb-Sdt localizes at the apical cell-cell contacts and plays roles in the formation of the tight junction and cell migration in mammalian cells. However it is not yet fully understood how PATJ has been localized to the apical cell junctions and its role in the regulation and maintenance of cell polarity. In this vivid study in elucidating functional significance of PATJ, a systematic structural-functional analysis have been carried out with deletion constructs tagged with green fluorescent protein (GFP) in transgenic flies to elucidate the roles of each conserved domain of the protein. In our study we found that the N-terminally located L27 domain along with a redundancy of the PDZ domains is required for proper functionality of the protein. Further we also found that PATJ attaches to both Baz-Sdt and Crb-Sdt complexes for its proper functionality. On our way to decipher how PATJ shuffles between these two complexes, we reveal the role of PAR6 in stabilizing Crb-Sdt complex via selective inhibition of Sdt degradation by ubiquitin mediated proteosomal pathway. Additionally we have found that PATJ is not per se crucial for the establishment or maintenance of apical-basal polarity, but rather regulates Myosin dynamics. PATJ directly binds to the Myosin Binding Subunit of Myosin Phosphatase and decreases Myosin dephosphorylation, resulting in activated Myosin dynamics. Thereby PATJ supports the stability of the Zonula Adherens. Notably, weakening of Adherens Junction (AJ) in a PATJ-mutant epithelium leads first to a loss of Myosin from the AJ, subsequently to a disassembly of the AJ and finally to a loss of apical-basal polarity and disruption of the tissue