Mutations of the 'discs large' (dlg) tumor suppressor locus in Drosophila lead to imaginal disc neoplasia and a prolonged larval period followed by death. Drosophila dlg and related proteins form a subfamily of the membrane-associated guanylate kinase (MAGUK) protein family and are important components of specialized cell junctions.
/////////Cloning and characterization of E-dlg, a novel splice variant of mouse homologue of the Drosophila discs large tumor suppressor binds preferentially to SAP102. Mao P et al. (2008) Membrane-associated guanylate kinases (MAGUKs) act as scaffolds to coordinate signaling events through their multiple domains at the plasma membrane. The MAGUK SH3 domain is noncanonical and its function remains unclear. To identify potential binding partners of MAGUK SH3, the synapse-associated protein 102 (SAP102) SH3 domain was used as bait in a yeast two-hybrid screen of a mouse embryonic cDNA library. A mouse homologue of the Drosophila discs large tumor suppressor (Dlg, also known as SAP97) bound preferentially to SAP102 SH3. The 4347bp cDNA sequence encoded an 893 amino acid protein with 94% identity to mouse SAP97. A deleted region (33-aa) strongly suggests this is a novel splice variant, which we call Embryonic-dlg/SAP97 (E-dlg). The interaction of SAP102 and E-dlg was confirmed in mammalian cells. E-dlg can also bind to potassium channel Kv1.4 in a pull-down assay. E-dlg was highly expressed in embryonic and some adult mouse tissues, such as brain, kidney, and ovary. Furthermore, in situ hybridization showed that E-dlg was mostly expressed in olfactory bulb and cerebellum.//////////////////
NCBI Summary:
This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene, but the full-length nature of some of the variants is not known. [provided by RefSeq, Feb 2011]
Discs large homologue 1 (Dlg1) coordinates mouse oocyte polarisation during maturation. Wang JC et al. (2016) Mouse oocyte meiotic division requires the establishment of asymmetries in the oocyte before division, indicating the presence of polarity-establishing molecules. During mouse oocyte maturation proper orientation and positioning of the meiotic spindle at the oocyte cortex, as well as polarity in the oocyte cytoplasm and its oolemma, are necessary for the formation of functional haploid oocytes. Discs large homologue 1 (Dlg1) protein is a conserved protein that regulates cell polarity. In the present study, we found that Dlg1 was expressed at different stages of oocyte development. The localisation of Dlg1 during mouse oocyte maturation and its relationship with the cytoskeleton were analysed. Our data show that at the germinal vesicle stage, Dlg1 was present in the cytoplasm, prominently surrounding the germinal vesicle membrane. During maturation, Dlg1 became highly polarised by associating with the spindle and formed characteristic crescent-shaped accumulations under the cortex. Addition of nocodazole or cytochalasin B into the culture medium at different stages changed the localisation of Dlg1, indicating that the organisation of Dlg1 is a complex multi-step process and is dependent on microtubules and microfilaments. More importantly, we found that silencing of Dlg1 compromised the G2-M transition.////////////////// ///////
Expression regulated by
Comment
PMID: 27651179
Ovarian localization
Oocyte, Granulosa
Comment
Expression and Distribution of Dlg1 during Meiotic Maturation in Mouse Oocytes. Wang JC et al. Mouse oocyte meiotic division requires the establishment of asymmetries in the oocyte prior to division, which implies the existence of polarity-establishing molecules. During mouse oocyte maturation correct orientation of the meiotic spindle and its positioning near the oocyte cortex, as well as the proper structural and molecular polarity of the oocyte cytoplasm and its oolemma, are necessary for the formation of the functional haploid oocyte. Discs, large homolog 1 (Dlg1) protein is a conserved protein that regulates cell polarity. Here, we find Dlg1 is expressed in different stages of oocytes at the mRNA and protein levels. We characterized the localization dynamics of Dlg1 during mouse oocyte maturation and analyzed its relationship with the cytoskeleton. At the germinal vesicle stage, Dlg1 is present in the cytoplasm, prominently surrounding the germinal vesicle membrane. During maturation, it becomes highly polarized by associating with the spindle and forms characteristic crescent-shaped accumulations under the cortex. Adding nocodazole and cytochalasm B into culture medium at different stages changes the localization of Dlg1. This indicates that the organization of Dlg1 is a complex multi-step process involving distinct microtubule- and microfilament-dependent phases.
Huang JH, et al 2003 reported the expression of Drosophila neoplastic tumor suppressor genes discslarge, scribble, and lethal giant larvae in the mammalian ovary.
The similarities and differences in molecular mechanisms regulating invertebrate and mammalian folliculogenesis are starting to be deciphered. In Drosophila, the neoplastic tumor suppressor gene discslarge is crucial for suppressing proliferation and movement of follicle cells relative to the growing oocyte. Lethal giant larvae and scribble play similar roles and have been suggested to collaborate intimately with discslarge. The authors have identified and determined the expression pattern of murine homologs of these Drosophila genes. In situ data shows that murine discslarge-1, discslarge-3, discslarge-4, lethal giant larvae, and scribble are expressed in both overlapping and distinct patterns in oocytes and granulosa cells in maturing follicles. Disclarge-4 is expressed in the surface epithelium and is lost in mouse carcinogenic surface epithelial cells. All of these genes, as well as discslarge-2 and discslarge-5, are expressed in human ovaries. The data suggests that as in Drosophila, these tumor suppressors may cooperate during mammalian folliculogenesis, but also have distinct functions.