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Fat and Expanded act in parallel to regulate growth through Warts

Author:
Feng, Yongqiang, Irvine, Kenneth D.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.51 pp. 20362-20367
ISSN:
0027-8424
Subject:
Drosophila melanogaster, insect proteins, regulatory proteins, protein kinases, protein-protein interactions, receptors, mutants, phenotype, mutation, cell growth
Abstract:
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.
Agid:
2354714