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Gene Review

dlg1  -  discs large 1

Drosophila melanogaster

Synonyms: 11, CG1725, CG1730, CPD, DLG, ...
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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


Anatomical context of dlg1


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


  1. The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila. Bellaïche, Y., Radovic, A., Woods, D.F., Hough, C.D., Parmentier, M.L., O'Kane, C.J., Bryant, P.J., Schweisguth, F. Cell (2001) [Pubmed]
  2. Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation. Koh, Y.H., Popova, E., Thomas, U., Griffith, L.C., Budnik, V. Cell (1999) [Pubmed]
  3. Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Bilder, D., Perrimon, N. Nature (2000) [Pubmed]
  4. Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein. Matsumine, A., Ogai, A., Senda, T., Okumura, N., Satoh, K., Baeg, G.H., Kawahara, T., Kobayashi, S., Okada, M., Toyoshima, K., Akiyama, T. Science (1996) [Pubmed]
  5. Synaptic clustering of the cell adhesion molecule fasciclin II by discs-large and its role in the regulation of presynaptic structure. Thomas, U., Kim, E., Kuhlendahl, S., Koh, Y.H., Gundelfinger, E.D., Sheng, M., Garner, C.C., Budnik, V. Neuron (1997) [Pubmed]
  6. A junctional problem of apical proportions: epithelial tube-size control by septate junctions in the Drosophila tracheal system. Wu, V.M., Beitel, G.J. Curr. Opin. Cell Biol. (2004) [Pubmed]
  7. Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Mathew, D., Gramates, L.S., Packard, M., Thomas, U., Bilder, D., Perrimon, N., Gorczyca, M., Budnik, V. Curr. Biol. (2002) [Pubmed]
  8. Novel spatiotemporal patterns of epithelial tumor invasion in Drosophila discs large egg chambers. Goode, S., Wei, J., Kishore, S. Dev. Dyn. (2005) [Pubmed]
  9. A Fasciclin 2 morphogenetic switch organizes epithelial cell cluster polarity and motility. Szafranski, P., Goode, S. Development (2004) [Pubmed]
  10. Regulation of synaptic plasticity and synaptic vesicle dynamics by the PDZ protein Scribble. Roche, J.P., Packard, M.C., Moeckel-Cole, S., Budnik, V. J. Neurosci. (2002) [Pubmed]
  11. Expression of Drosophila neoplastic tumor suppressor genes discslarge, scribble, and lethal giant larvae in the mammalian ovary. Huang, J.H., Rajkovic, A., Szafranski, P., Ochsner, S., Richards, J., Goode, S. Gene Expr. Patterns (2003) [Pubmed]
  12. Organizing a functional junctional complex requires specific domains of the Drosophila MAGUK Discs large. Hough, C.D., Woods, D.F., Park, S., Bryant, P.J. Genes Dev. (1997) [Pubmed]
  13. Cell type-specific recruitment of Drosophila Lin-7 to distinct MAGUK-based protein complexes defines novel roles for Sdt and Dlg-S97. Bachmann, A., Timmer, M., Sierralta, J., Pietrini, G., Gundelfinger, E.D., Knust, E., Thomas, U. J. Cell. Sci. (2004) [Pubmed]
  14. Discs-large (DLG) is clustered by presynaptic innervation and regulates postsynaptic glutamate receptor subunit composition in Drosophila. Chen, K., Featherstone, D.E. BMC Biol. (2005) [Pubmed]
  15. The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migration. Six, E.M., Ndiaye, D., Sauer, G., Laâbi, Y., Athman, R., Cumano, A., Brou, C., Israël, A., Logeat, F. J. Biol. Chem. (2004) [Pubmed]
  16. Coordinating structural and functional synapse development: postsynaptic p21-activated kinase independently specifies glutamate receptor abundance and postsynaptic morphology. Albin, S.D., Davis, G.W. J. Neurosci. (2004) [Pubmed]
  17. Integrins regulate DLG/FAS2 via a CaM kinase II-dependent pathway to mediate synapse elaboration and stabilization during postembryonic development. Beumer, K., Matthies, H.J., Bradshaw, A., Broadie, K. Development (2002) [Pubmed]
  18. Localization of PDZ domain containing proteins Discs Large-1 and Scribble in the mouse eye. Nguyen, M.M., Rivera, C., Griep, A.E. Mol. Vis. (2005) [Pubmed]
  19. Discs-Large and Strabismus are functionally linked to plasma membrane formation. Lee, O.K., Frese, K.K., James, J.S., Chadda, D., Chen, Z.H., Javier, R.T., Cho, K.O. Nat. Cell Biol. (2003) [Pubmed]
  20. Epithelial polarity and cell separation in the neoplastic l(1)dlg-1 mutant of Drosophila. Abbott, L.A., Natzle, J.E. Mech. Dev. (1992) [Pubmed]
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