Fat cadherins in the regulation of planar polarity, tissue growth and mitochondrial activity


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Helen McNeill1
1University of Toronto and Lunenfeld-Tanenbaum Institute of Mount Sinai Hospital, Toronto, Canada

Abstract

Fat cadherins are enormous cell adhesion molecules (560kDa) that planar polarity, tissue growth and spindle orientation during development. Fat cadherins are highly conserved from Drosophila to man. Fat cadherins do not bind to other Fat cadherins, but instead bind another large cadherin, Dachsous. Fat-Dachsous binding regulates activity of the Hippo kinase pathway, a well known and highly conserved growth regulatory pathway. Fat-Dachsous interactions also regulate planar polarity, and loss of planar polarity leads to cystic disease in mouse models. The mechanisms by which Fat regulates planar polarity and growth are still poorly understood. Using yeast two hybrid analysis, proteomic screens and genetic screens in Drosophila, we have recently identified an essential role for Fat cadherins in the regulation of mitochondrial activity. These studies indicate a direct role for Fat in control of cellular energy and ROS signalling in normal development, and suggest how loss of Fat function may contribute to human diseases.