Abstract

The HMP1-HMP2 protein complex, a counterpart of -catenin-{beta}-catenin complex in C. elegans, mediates the tension transmission between HMR1 (cadherin) and actin cytoskeleton and serves as a critical mechanosensor at the cell-cell adherens junction. The complex has been shown to play critical roles in embryonic development and tissue integrity in C. elegans. The complex is subject to tension due to internal actomyosin contractility and external mechanical micro-environmental perturbations. However, how tension regulates the stability and interaction of HMP1-HMP2 complex has yet to be investigated. Here, we directly quantify the mechanical stability of the full-length HMP1 and its force-bearing modulation domains (M1-M3), and show that they unfold within physiological level of tension (pico-newton scale). The inter-domain interactions within the modulation domain leads to strong mechanical stabilization of M1 in HMP1, resulting in a significantly stronger force threshold to expose the buried vinculin binding site compared to the M1 domain in -catenins. Moreover, we also quantify the mechanical stability of the inter-molecular HMP1-HMP2 interface and show that it is mechanically stable enough to support the tension-transmission and tension-sensing of the HMP1 modulation domains. Further, we show that single-residue phosphomimetic mutation (Y69E) on HMP2 weakens the mechanical stability of the HMP1-HMP2 interface and thus weakens the force-transmission molecular linkage and the associated mechanosensing functions. Together, these results provide a mechano-biochemical understanding of C. elegans HMP1-HMP2 protein complexs roles in mechanotransduction.