Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster

Abstract

Background Scaffold proteins support a variety of key processes during animal development. Mutant mouse for the MAGUK protein Discs large 5 (Dlg5) presents a general growth impairment and moderate morphogenetic defects. Results Here, we generated null mutants for Drosophila Dlg5 and show that it owns similar functions in growth and epithelial architecture. Dlg5 is required for growth at a cell autonomous level in several tissues and at the organism level, affecting cell size and proliferation. Our results are consistent with Dlg5 modulating hippo pathway in the wing disc, including the impact on cell size, a defect that is reproduced by the loss of yorkie. However, other observations indicate that Dlg5 regulates growth by at least another way that may involve Myc protein but nor PI3K neither TOR pathways. Moreover, epithelia cells mutant for Dlg5 also show a reduction of apical domain determinants, though not sufficient to induce a complete loss of cell polarity. Dlg5 is also essential, in the same cells, for the presence at Adherens junctions of N-Cadherin, but not E-Cadherin. Genetic analyses indicate that junction and polarity defects are independent. Conclusions Together our data show that Dlg5 own several conserved functions that are independent of each other in regulating growth, cell polarity and cell adhesion. Moreover, they reveal a differential regulation of E-cadherin and N-cadherin apical localization.

Transcellular chaperone signaling is an intercellular stress-response distinct from the HSF-1–mediated heat shock response

“…Our data shows that TXT-1 and CEH-58 genetically interact as part of an intracellular signaling cue in the C. elegans body wall muscle, corroborating a previous yeast-two-hybrid study that demonstrated direct interaction between both proteins [38]. Although our study is the first to note an association of TXT-1 with the heat stress response in C. elegans, its closest human orthologue, DLG5, is a membrane associated guanylate cyclase that is part of the Hippo pathway [59,60] and is involved in the cellular response to heat stress [61].…”

Transcriptomic Changes Following Induced De-Masculinisation of Australian Red Claw Crayfish Cherax quadricarinatus

“…Highly conserved between vertebrates and invertebrates, DLG5 is a scaffold protein with multiple functions, including cell growth, polarity, and adhesion. Knockdown of DLG5 in Drosophila melanogaster has been shown to cause a reduction in wing growth targeting cell proliferation [ 56 ]. In the testis histology images ( Figure 5 ), it can be seen that there are many spermatogonia in the Cq-IAG -silenced group, but they do not appear to be progressing to mature spermatozoa as seen in the healthy control testis.…”

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia

“…In vitro studies have reported that PFKFB3-kinase activity attenuates the activation of T cells, and demonstrated the effectiveness of PFKFB3 antagonists, even in small amounts, as T cell immunosuppressive agents (55). One of the differentially expressed genes, KLF9, has been previously identified as differentially expressed in T cells from patients with autoimmune rheumatoid arthritis (56), while another, DLG5, is involved in the HIPPO pathway and modulated TGFB signaling (57)(58)(59).…”