TRIP6 is required for tension at adherens junctions

Abstract

Hippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6and LIMD1 have each been identified as being required for tension-dependent inhibition of the Hippo pathway LATS kinases and their recruitment to adherens junctions, but the relationship between TRIP6 and LIMD1 was unknown. Using siRNA-mediated gene knockdown we show that TRIP6 is required for LIMD1 localization to adherens junctions, whereas LIMD1 is not required for TRIP6 localization. TRIP6, but not LIMD1, is also required for recruitment of Vinculin and VASP to adherens junctions. Knockdown of TRIP6 or Vinculin, but not of LIMD1, also influences the localization of phosphorylated myosin light chain and F-actin. In TRIP6 knockdown cells actin stress fibers are lost apically but increased basally, and there is a corresponding increase in recruitment of Vinculin and VASP to basal focal adhesions. These observations identify a role for TRIP6 in organizing F-actin and maintaining tension at adherens junctions that could account for its influence on LIMD1 and LATS. They also suggest that focal adhesions and adherens junctions compete for key proteins needed to maintain attachments to contractile F-actin.

Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

“…Mechanical forces at cell-cell junctions also control YAP/TAZ, as strain on epithelial monolayers induce β-catenin and YAP1 nuclear localization ( 62 , 63 ). Moreover, high tension inferred at the junctional cadherin-catenin complex, triggers the interaction of α-catenin with TRIP6 and LIMD1, which recruit LATS1/2 to the junctions and inhibit their kinase activity, leading to nuclear translocation of YAP/TAZ ( 64 – 66 ). The various Hippo and mechanotransduction pathways that regulate YAP/TAZ have been elegantly discussed previously ( 45 , 63 , 67 , 68 ).…”