Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
Posted 12 May, 2020
On 24 Apr, 2020
On 14 Apr, 2020
On 13 Apr, 2020
On 13 Apr, 2020
On 25 Mar, 2020
On 22 Mar, 2020
Received 22 Mar, 2020
Received 22 Mar, 2020
On 17 Mar, 2020
Received 15 Mar, 2020
Invitations sent on 09 Mar, 2020
On 09 Mar, 2020
On 25 Feb, 2020
On 24 Feb, 2020
On 24 Feb, 2020
On 24 Feb, 2020
Multiple functions of the scaffold protein Discs large 5 in the control of growth, cell polarity and cell adhesion in Drosophila melanogaster
Posted 12 May, 2020
On 24 Apr, 2020
On 14 Apr, 2020
On 13 Apr, 2020
On 13 Apr, 2020
On 25 Mar, 2020
On 22 Mar, 2020
Received 22 Mar, 2020
Received 22 Mar, 2020
On 17 Mar, 2020
Received 15 Mar, 2020
Invitations sent on 09 Mar, 2020
On 09 Mar, 2020
On 25 Feb, 2020
On 24 Feb, 2020
On 24 Feb, 2020
On 24 Feb, 2020
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6