Deciphering molecular mechanism of adherens junction mechanosensitivity

It is well established that integrin-mediated adhesions (such as focal adhesions) are mechano-responsive: they grow when force is applied to them and they disassemble when tension is relieved. Stretching of cas and talin, exposing vinculin binding sites, recruitment of LIM domain proteins and tyrosine dephosphorylation of paxillin have all been implicated in integrin-mediated mechanosensing.

In recent years it is becoming apparent that adherens junctions are also sensitive to the level of tension at the junction. Inhibition of tension leads to disassembly of adherens junctions (albeit at a slower rate compared to focal adhesions), and increasing contractility within cells (by activating RhoA, for example) leads to reinforement of the junctions. The one mechanism proposed to date for junctional mechanosensing is the stretching of alpha-catenin by force, exposing a binding site for vinculin. We are working towards identifying novel components responsible for force-induced junction assembly by two methods: 1. An siRNA screen of candidate genes applied to a robust assay for force-induced assembly. 2. Differential mass spectroscopy of isolated cadherin adhesions under high and low tension conditions.