RRC ID 78336
Author Portela M, Mukherjee S, Paul S, La Marca JE, Parsons LM, Veraksa A, Richardson HE.
Title The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.
Journal J Cell Sci
Abstract The tumour suppressor, Lethal (2) giant larvae [Lgl; also known as L(2)gl], is an evolutionarily conserved protein that was discovered in the vinegar fly Drosophila, where its depletion results in tissue overgrowth and loss of cell polarity. Lgl links cell polarity and tissue growth through regulation of the Notch and the Hippo signalling pathways. Lgl regulates the Notch pathway by inhibiting V-ATPase activity via Vap33. How Lgl regulates the Hippo pathway was unclear. In this current study, we show that V-ATPase activity inhibits the Hippo pathway, whereas Vap33 acts to activate Hippo signalling. Vap33 physically and genetically interacts with the actin cytoskeletal regulators RtGEF (Pix) and Git, which also bind to the Hippo protein (Hpo) and are involved in the activation of the Hippo pathway. Additionally, we show that the ADP ribosylation factor Arf79F (Arf1), which is a Hpo interactor, is involved in the inhibition of the Hippo pathway. Altogether, our data suggest that Lgl acts via Vap33 to activate the Hippo pathway by a dual mechanism: (1) through interaction with RtGEF, Git and Arf79F, and (2) through interaction and inhibition of the V-ATPase, thereby controlling epithelial tissue growth.
Volume 137(4)
Published 2024-2-15
DOI 10.1242/jcs.261917
PII 342469
PMID 38240353
PMC PMC10911279
MeSH Adenosine Triphosphatases / metabolism Animals Cell Polarity Drosophila / metabolism Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster Hippo Signaling Pathway Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Neoplasms* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Signal Transduction Tumor Suppressor Proteins / metabolism
Drosophila DGRC#115288