Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Development 140 (4): 831-842

RESEARCH ARTICLES

Signal transduction by the Fat cytoplasmic domain

Guohui Pan, Yongqiang Feng*, Abhijit A. Ambegaonkar, Gongping Sun, Matthew Huff, Cordelia Rauskolb, and Kenneth D. Irvine{ddagger}

Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers The State University of New Jersey, Piscataway, NJ 08854, USA.

{ddagger} Author for correspondence (irvine{at}waksman.rutgers.edu)

Accepted for publication 3 December 2012.

Abstract: The large atypical cadherin Fat is a receptor for both Hippo and planar cell polarity (PCP) pathways. Here we investigate the molecular basis for signal transduction downstream of Fat by creating targeted alterations within a genomic construct that contains the entire fat locus, and by monitoring and manipulating the membrane localization of the Fat pathway component Dachs. We establish that the human Fat homolog FAT4 lacks the ability to transduce Hippo signaling in Drosophila, but can transduce Drosophila PCP signaling. Targeted deletion of conserved motifs identifies a four amino acid C-terminal motif that is essential for aspects of Fat-mediated PCP, and other internal motifs that contribute to Fat-Hippo signaling. Fat-Hippo signaling requires the Drosophila Casein kinase 1{epsilon} encoded by discs overgrown (Dco), and we characterize candidate Dco phosphorylation sites in the Fat intracellular domain (ICD), the mutation of which impairs Fat-Hippo signaling. Through characterization of Dachs localization and directed membrane targeting of Dachs, we show that localization of Dachs influences both the Hippo and PCP pathways. Our results identify a conservation of Fat-PCP signaling mechanisms, establish distinct functions for different regions of the Fat ICD, support the correlation of Fat ICD phosphorylation with Fat-Hippo signaling, and confirm the importance of Dachs membrane localization to downstream signaling pathways.

Key Words: Dachsous • Drosophila • Fat • Hippo • PCP • Polarity

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Signal transduction by the Fat cytoplasmic domain.
G. Pan, Y. Feng, A. A. Ambegaonkar, G. Sun, M. Huff, C. Rauskolb, and K. D. Irvine (2013)
J. Cell Sci. 126, e1
   Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882