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

Parvathy Venugopal,Caroline Vachias,Jean-Louis Couderc,Hugo Veyssière,Graziella Richard,Vincent Mirouse

doi:10.1186/s12861-020-00218-0

Abstract

BackgroundScaffold 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.ResultsHere, 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.ConclusionsTogether 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.

Highlights

Scaffold proteins support a variety of key processes during animal development
The loss of Discs large 5 (Dlg5) alters cell autonomously follicle cell growth We performed a reverse genetics screen to identify new genes involved in Drosophila follicular epithelium development, a tissue used as a generic model for various aspects of epithelium biology [18, 19]
We noticed that clones expressing RNAi against Dlg5 were small and the cells appeared smaller than wild-type cells, especially after stage 6 (Fig. 1a)

Summary

Introduction

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. Among the protein classes involved in such processes, many of them are scaffold proteins. These proteins are devoid of catalytic activity but contain multiple domains of protein-protein. Membrane-associated guanylate kinase (MAGUK) proteins are typical examples of scaffold proteins [2]. MAGUK domain is a structural unit formed by SH3 domain next to a non-catalytically active guanylate kinase domain. These domains are usually flanked by one or several PDZ domains and potentially other proteinprotein interaction domains.

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