RhoGEF2 overexpression induces cell competition dependent on Ptp10D, Crumbs and the Hippo signaling pathway

Fahey-Lozano, N; Portela, M; La Marca, JE; Richardson, HE

Author(s): Fahey-Lozano, N; Portela, M; La Marca, JE; Richardson, HE;
Details: Publication Year 2025-10-01,Volume 138,Issue #19,Page jcs264377
Journal Title: Journal of Cell Science
Abstract: In Drosophila melanogaster larval epithelial tissues, cells containing mutations in the apico-basal polarity protein, Scrib, are eliminated by cell competition when surrounded by wild-type cells. In scrib mutant cells, signaling mediated by the receptor-type tyrosine phosphatase Ptp10D upon engagement with its ligand Sas in the surrounding wild-type cells triggers cell competition via EGFR-Ras pathway inhibition and JNK pathway activation, which induces apoptosis of the mutant cells. Here, we investigate whether overexpression of RhoGEF2 (RhoGEF2OE), which induces Rho signaling and affects actin cytoskeleton regulators, acts similarly to Scrib depletion in cell competition. We show that RhoGEF2OE cells are eliminated when surrounded by wild-type cells and that Ptp10D knockdown increases RhoGEF2OE clone growth. Mechanistically, in clones moderately overexpressing RhoGEF2OE, Ptp10D knockdown rescued cell elimination by reducing Hippo signaling. Additionally, mutations in the apical cell polarity protein, Crb, partially rescued the elimination of RhoGEF2OE clones. In this setting, in which RhoGEF2OE is highly overexpressed, JNK and Hippo signaling were elevated whereas EGFR-Ras signaling was reduced, and crb loss normalized these pathways. Thus, RhoGEF2OE leads to clone elimination dependent on Crb, Ptp10D and Hippo signaling.
Publisher: COB
Keywords: Animals; *Drosophila Proteins/metabolism/genetics; *Drosophila melanogaster/metabolism/genetics/cytology; Signal Transduction; *Protein Serine-Threonine Kinases/metabolism/genetics; *Membrane Proteins/metabolism/genetics; *Intracellular Signaling Peptides and Proteins/metabolism/genetics; *Protein Tyrosine Phosphatases/metabolism/genetics; *Eye Proteins/metabolism/genetics; Cell Polarity; ErbB Receptors/metabolism; Mutation; Hippo Signaling Pathway; Drosophila; Cell competition; Crumbs; Hippo; Ptp10D; RhoGEF2
Research Division(s): Blood Cells and Blood Cancer
PubMed ID: 40968980
Publisher's Version: https://doi.org/10.1242/jcs.264377
Open Access at Publisher's Site: https://doi.org/10.1242/jcs.264377
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-10-20 01:57:43

Last Modified: 2025-10-20 01:57:58