The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila.

Details

Serval ID
serval:BIB_8A49754F6693
Type
Article: article from journal or magazin.
Collection
Publications
Title
The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in Drosophila.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Chen C.L., Gajewski K.M., Hamaratoglu F., Bossuyt W., Sansores-Garcia L., Tao C., Halder G.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
2010
Volume
107
Number
36
Pages
15810-15815
Language
english
Notes
h
Abstract
Defects in apical-basal cell polarity and abnormal expression of cell polarity determinants are often associated with cancer in vertebrates. In Drosophila, abnormal expression of apical-basal determinants can cause neoplastic phenotypes, including loss of cell polarity and overproliferation. However, the pathways through which apical-basal polarity determinants affect growth are poorly understood. Here, we investigated the mechanism by which the apical determinant Crumbs (Crb) affects growth in Drosophila imaginal discs. Overexpression of Crb causes severe overproliferation, and we found that loss of Crb similarly results in overgrowth of imaginal discs. Crb gain and loss of function caused defects in Hippo signaling, a key signaling pathway that controls tissue growth in Drosophila and mammals. Manipulation of Crb levels caused the up-regulation of Hippo target genes, genetically interacted with known Hippo pathway components, and required Yorkie, a transcriptional coactivator that acts downstream in the Hippo pathway, for target gene induction and overgrowth. Interestingly, Crb regulates growth and cell polarity through different motifs in its intracellular domain. A juxtamembrane FERM domain-binding motif is responsible for growth regulation and induction of Hippo target gene expression, whereas Crb uses a PDZ-binding motif to form a complex with other polarity factors. The Hippo pathway component Expanded, an apically localized adaptor protein, is mislocalized in both crb mutant cells and Crb overexpressing tissues, whereas the other Hippo pathway components, Fat and Merlin, are unaffected. Taken together, our data show that Crb regulates growth through Hippo signaling, and thus identify Crb as a previously undescribed upstream input into the Hippo pathway.
Keywords
Animals, Cell Polarity/physiology, Cell Proliferation, Drosophila, Drosophila Proteins/metabolism, Drosophila Proteins/physiology, Intracellular Signaling Peptides and Proteins/metabolism, Membrane Proteins/physiology, Protein-Serine-Threonine Kinases/metabolism, Signal Transduction/physiology
Pubmed
Web of science
Open Access
Yes
Create date
06/02/2014 17:44
Last modification date
20/08/2019 14:49
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