Rho GTPase controls Drosophila salivary gland lumen size through regulation of the actin cytoskeleton and Moesin

Abstract

SUMMARYGeneration and maintenance of proper lumen size is important for tubular organ function. We report on a novel role for the Drosophila Rho1 GTPase in control of salivary gland lumen size through regulation of cell rearrangement, apical domain elongation and cell shape change. We show that Rho1 controls cell rearrangement and apical domain elongation by promoting actin polymerization and regulating F-actin distribution at the apical and basolateral membranes through Rho kinase. Loss of Rho1 resulted in reduction of F-actin at the basolateral membrane and enrichment of apical F-actin, the latter accompanied by enrichment of apical phosphorylated Moesin. Reducing cofilin levels in Rho1 mutant salivary gland cells restored proper distribution of F-actin and phosphorylated Moesin and rescued the cell rearrangement and apical domain elongation defects of Rho1 mutant glands. In support of a role for Rho1-dependent actin polymerization in regulation of gland lumen size, loss of profilin phenocopied the Rho1 lumen size defects to a large extent. We also show that Ribbon, a BTB domain-containing transcription factor functions with Rho1 in limiting apical phosphorylated Moesin for apical domain elongation. Our studies reveal a novel mechanism for controlling salivary gland lumen size, namely through Rho1-dependent actin polymerization and distribution and downregulation of apical phosphorylated Moesin.

Integration of actomyosin contractility with cell-cell adhesion during dorsal closure

“…We do not know how Mbs regulates DE-Cadherin dynamics, but it may involve Moesin function. Consistent with our results that an increase in the levels of phosphorylated Moesin could prevent proper junction remodelling in mbs mutant embryos, is the observation that increased apical Moesin activity prevents cell shape changes during the morphogenesis of salivary glands (Xu et al, 2011). Thus, our results suggest that the levels of phosphorylated Moesin must be tightly controlled to allow for the rapid cell shape changes AS cells are undergoing during late DC.…”

Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression

“…3D,E). Since SG shape is also dependent on how the cells are arranged around the lumen (Chung and Andrew, 2014; Pirraglia et al, 2013; Xu et al, 2011), we analyzed cell arrangement by examining the cross-sectional images obtained along the luminal axis (Fig. 3D, E).…”

Development of apical membrane organization and V-ATPase regulation in blowfly salivary glands

“…Members of the ERM (ezrin/radixin/moesin) protein family play a crucial role in the morphogenesis and organization of the apical domain of epithelial cells (Bretscher et al, 1997;Fehon et al, 2010), including the larval salivary gland of Drosophila (Xu et al, 2011). Typically, ERM proteins consist of an N-terminal domain that binds to phospholipids and membrane proteins, an α-helical domain, and a C-terminal F-actin-binding domain.…”

“…In Drosophila, the latter step is mediated by the sterile 20 family kinase Slik (Hipfner et al, 2004). It has been proposed that activated Drosophila moesin influences the organization of the cortical cytoskeleton by acting antagonistically to the Rho signalling pathway (Speck et al, 2003;Xu et al, 2011). Notably, Slik and Rho signalling components seem to be expressed at a high level in the adult Drosophila salivary gland (Chintapalli et al, 2007).…”