Identification and characterization of genetic interactors of the Rho Guanine-nucleotide exchange factor Pebble in Drosophila
type: CreativeWork
description: The gene pebble (pbl) encodes a Rho GEF required for the migration of mesoderm cells during Drosophila gastrulation. The spreading of mesoderm cells is controlled by the FGF signalling pathway acting through the FGF receptor Heartless (Htl). Pbl represents an important downstream component of this FGF pathway and activates the Rho GTPase Rac, but the regulation of Pbl by FGF signalling is unclear. Furthermore Pbl is required for the formation of the actin-myosin contractile ring during cytokinesis by activation of RhoA. The purpose of this work is to find molecular links between Pbl and the Htl signalling pathway and get insight into the localization and regulation of Pbl during mesoderm cell migration A genetic screen is carried out to find genes that interact with Pbl and are involved in mesoderm development. A gain-of-function variant of Pbl that causes defects in eye morphology was used to find genetic interactors. Results of a screen using chromosomal deletions and an EMS-based screen revealed candidates, which genetically interact with Pbl and are required for mesoderm cell migration. In addition, a structure-function analysis of the Pbl protein was performed. The data revealed an important role of the PH domain for the localization of Pbl at the cell cortex. Moreover the PH domain is indispensable for the function of Pbl in mesoderm migration. Furthermore an important role for the C-terminal tail of Pbl for the regulation of the protein was shown, which might be regulated by FGF signalling. The C-terminal tail is required for the stability of the protein outside the nucleus and it regulates the substrate preference of Pbl for Rac and Rho. Furthermore indication was found that the function of the C-terminal tail possibly is regulated by phosphorylation of Ser825 in the C-terminal tail. Mutation of this site affects the function of Pbl during mesoderm migration but not in cytokinesis. Therefore phosphorylation of the C-terminal tail might regulate or enhance th…
abstract: The gene pebble (pbl) encodes a Rho GEF required for the migration of mesoderm cells during Drosophila gastrulation. The spreading of mesoderm cells is controlled by the FGF signalling pathway acting through the FGF receptor Heartless (Htl). Pbl represents an important downstream component of this FGF pathway and activates the Rho GTPase Rac, but the regulation of Pbl by FGF signalling is unclear. Furthermore Pbl is required for the formation of the actin-myosin contractile ring during cytokinesis by activation of RhoA. The purpose of this work is to find molecular links between Pbl and the Htl signalling pathway and get insight into the localization and regulation of Pbl during mesoderm cell migration A genetic screen is carried out to find genes that interact with Pbl and are involved in mesoderm development. A gain-of-function variant of Pbl that causes defects in eye morphology was used to find genetic interactors. Results of a screen using chromosomal deletions and an EMS-based screen revealed candidates, which genetically interact with Pbl and are required for mesoderm cell migration. In addition, a structure-function analysis of the Pbl protein was performed. The data revealed an important role of the PH domain for the localization of Pbl at the cell cortex. Moreover the PH domain is indispensable for the function of Pbl in mesoderm migration. Furthermore an important role for the C-terminal tail of Pbl for the regulation of the protein was shown, which might be regulated by FGF signalling. The C-terminal tail is required for the stability of the protein outside the nucleus and it regulates the substrate preference of Pbl for Rac and Rho. Furthermore indication was found that the function of the C-terminal tail possibly is regulated by phosphorylation of Ser825 in the C-terminal tail. Mutation of this site affects the function of Pbl during mesoderm migration but not in cytokinesis. Therefore phosphorylation of the C-terminal tail might regulate or enhance th…
author: Draga, Margarethe Maria
language: eng
keywords: Drosophila, RhoGEF, Mesoderm, Cell migration
date published: 2010
date modified: 2026-07-24T02:07:31Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee