Crumbs acts via the FERM-domain protein Expanded to regulate Salvador/Warts/Hippo signaling in Drosophila

• Type of Material: Article
• Authors: Brian S. Robinson, Emory University; Juang Huang, University of Pittsburgh; Yang Hong, University of Pittsburgh; Kenneth H. Moberg, Emory University
• Language: English
• Date: 2010-04-13
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cub.2010.03.019
• Title of Journal or Parent Work: Current Biology
• ISSN: 0960-9822
• Volume: 20
• Issue: 7
• Start Page: 582
• End Page: 590
• Grant/Funding Information: This work was supported by RO1 CA123368 (KHM) and NIH T32 GM008367 (BSR).
• Research Categories: Biology, Cell

Abstract

Summary Background Altered expression of apicobasal polarity factors is associated with cancer in vertebrates and tissue overgrowth in invertebrates, yet mechanisms by which these factors affect growth regulatory pathways are not well defined. We have tested the basis of an overgrowth phenotype driven by the Drosophila protein Crumbs (Crb), which nucleates an apical membrane complex that functionally interacts with the Par6/Par3/aPKC and Scrib/Dlg/Lgl apicobasal polarity complexes. Results We find that Crb-driven growth is dependent upon the Salvador-Warts-Hippo (SWH) pathway and its transcriptional effector Yorkie (Yki). Expression of the Crb intracellular domain elevates Yki activity and this correlates in tissues and cultured cells with loss of Expanded (Ex), an apically localized SWH component that inhibits Yki. Reciprocally, loss of crb elevates Ex levels, although this excess Ex does not concentrate to its normal location at apical junctions. The Ex-regulatory domain of Crb maps to the juxtamembrane FERM-domain binding motif (JM), a cytoskeletal interaction domain distinct from the PDZ-binding motif (PBM) through which Crb binds polarity factors. Expression of Crb-JM drives Yki activity and organ growth with little effect on tissue architecture, while reciprocally Crb-PBM produces tissue architectural defects without significant effect on Yki activity. Conclusions These studies identify Crb as a novel SWH regulator via JM-dependent effects on Ex levels and localization, and show that discrete domains within Crb may allow it to integrate junctional polarity signals with a conserved growth pathway.