High impact information on dlg1

• The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila [1].
• In vitro, CaMKII phosphorylated a DLG fragment with a stoichiometry close to one [2].
• Mutations in Drosophila scribble (scrib), which encodes a multi-PDZ (PSD-95, Discs-large and ZO-1) and leucine-rich-repeat protein, cause aberrant cell shapes and loss of the monolayer organization of embryonic epithelia [3].
• APC colocalized with DLG at the lateral cytoplasm in rat colon epithelial cells and at the synapse in cultured hippocampal neurons [4].
• These results suggest that the APC-DLG complex may participate in regulation of both cell cycle progression and neuronal function [4].

Biological context of dlg1

• These results indicate a central role for DLG in the structural organization and downstream signaling mechanisms of cell adhesion molecules and ion channels at synapses [5].
• Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation [2].
• Possible tube-size functions of septate junctions include patterning of the apical extracellular matrix and regulation of conserved cell polarity genes such as Scribble and Discs Large [6].
• Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein [7].
• Loss of Discslarge (Dlg) in early Drosophila egg chambers causes invasion of tumor follicle cells from the anterior epithelium, a pattern that resembles developmental border cell migration during mid-oogenesis [8].

Anatomical context of dlg1

• This polarity switch, which is organized in collaboration with neoplastic tumor suppressors Discs large and Lethal-giant-larvae, directs cluster asymmetry essential for timing delamination from the epithelium [9].
• At the larval neuromuscular junction, Scrib colocalizes and indirectly interacts with another tumor suppressor and PDZ protein, Discs-Large (Dlg) [10].
• RESULTS: Here we report the isolation of a new DLG-interacting protein, GUK-holder, that interacts with the GUK domain of DLG and which is dynamically expressed during synaptic bouton budding [7].
• In Drosophila, the neoplastic tumor suppressor gene discslarge is crucial for suppressing proliferation and movement of follicle cells relative to the growing oocyte [11].
• Discs large (Dlg) was the first identified member of an increasingly important class of proteins called membrane-associated guanylate kinase homologs (MAGUKs), which are often concentrated at cell junctions and contain distinct peptide domains named PDZ1-3, SH3, HOOK, and GUK [12].

Associations of dlg1 with chemical compounds

• Stardust (Sdt) and Discs-Large (Dlg) are membrane-associated guanylate kinases (MAGUKs) involved in the organization of supramolecular protein complexes at distinct epithelial membrane compartments in Drosophila [13].
• We also show that DLG, like glutamate receptors, is localized only after the presynaptic neuron contacts the postsynaptic cell [14].
• Dlg1 is a human homolog of the Drosophila Discs large tumor suppressor, a member of the membrane-associated guanylate kinase family of molecular scaffolds [15].

Co-localisations of dlg1

• We also show that at Drosophila synapses DLG colocalizes with SCRIB and that this colocalization is likely to be mediated by direct interactions between GUKH and the PDZ2 domain of SCRIB [7].

Regulatory relationships of dlg1

• Here we demonstrate that synaptic localization of DLG itself is regulated by CaMKII [2].
• We hypothesize that glutamate receptors and DLG cluster in response to parallel signals from the presynaptic neuron, after which DLG regulates subunit composition by stabilizing (probably indirectly) receptors that contain the GluRIIB subunit [14].
• A second genetically separable function of Pak kinase signaling controls muscle membrane specialization through the regulation of synaptic Discs-large [16].

Other interactions of dlg1

• Integrins regulate DLG/FAS2 via a CaM kinase II-dependent pathway to mediate synapse elaboration and stabilization during postembryonic development [17].
• Localization of PDZ domain containing proteins Discs Large-1 and Scribble in the mouse eye [18].
• Here we show that this important process depends on a functional complex formed between the tumour suppressor and adaptor protein Discs-Large (Dlg) and the integral membrane protein Strabismus (Stbm)/Van Gogh (Vang) [19].
• Fas2-mediated communication between polar and border cells maintains localization of Discs large and Lethal-giant-larvae in border cells to inhibit the rate of cluster migration [9].
• The finding that Discs large and Lethal-giant-larvae inhibit the rate of normal cell cluster movement suggests that their loss in metastatic tumors may directly contribute to tumor motility [9].

Analytical, diagnostic and therapeutic context of dlg1

• Here, we use immunohistochemistry, confocal microscopy, and electrophysiology to examine whether fly NMJ glutamate receptor clusters form normally in DLG mutants [14].
• Epithelial polarity and cell separation in the neoplastic l(1)dlg-1 mutant of Drosophila [20].

References