Fat and Expanded act in parallel to regulate growth through Warts

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 51; pp. 20362 - 20367
• Main Authors: Feng, Yongqiang, Irvine, Kenneth D
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.12.2007; National Acad Sciences
• Subjects: Additive effects; Animals; Biological Sciences; Cadherins; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; cell growth; Cells; Drosophila; Drosophila - growth & development; Drosophila - metabolism; Drosophila melanogaster; Drosophila Proteins - analysis; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Expanded protein; Fat protein; Fats; Gene expression; Gene expression regulation; Genetic mutation; insect proteins; Intracellular Signaling Peptides and Proteins; Membrane Proteins - analysis; Membrane Proteins - genetics; Membrane Proteins - metabolism; mutants; Mutation; Noise reduction; phenotype; Phenotypes; protein kinases; Protein Kinases - genetics; Protein Kinases - metabolism; Protein Serine-Threonine Kinases - metabolism; protein-protein interactions; Proteins; protocadherin; receptors; regulatory proteins; Signal transduction; tumor suppressors; Tumors; Warts; Warts protein
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0706722105

The conserved Drosophila tumor suppressors Fat and Expanded have both recently been implicated in regulating the activity of the Warts tumor suppressor. However, there has been disagreement as to the nature of the links among Fat, Expanded, and Warts and the significance of these links to growth control. We report here that mutations in either expanded or fat can be rescued to viability simply by overexpressing Warts, indicating that their essential function is their influence on Warts rather than reported effects on endocytosis or other pathways. These rescue experiments also separate the transcriptional from the planar cell polarity branches of Fat signaling and reveal that Expanded does not directly affect polarity. We also investigate the relationship between expanded and fat and show, contrary to prior reports, that they have additive effects on imaginal disk growth and development. Although mutation of fat can cause partial loss of Expanded protein from the membrane, mutation of fat promotes growth even when Expanded is overexpressed and accumulates at its normal subapical location. These observations argue against recent proposals that Fat acts simply as a receptor for the Hippo signaling pathway and instead support the proposal that Fat and Expanded can act in parallel to regulate Warts through distinct mechanisms.