The synovial cadherin (cadherin-11) promotes intercellular motility

Cadherin-11 is a homophilic adhesion molecule that is expressed on fibroblast-like synoviocytes. Cadherins mediate tissue morphogenesis and architecture. Cadherin cell adhesion contacts are actively remodeled and impact cell movement and migration over other cells. To determine the molecular mechanisms that contribute to cadherin-11-dependent cell migration, we generated cadherin-11 mutants. We found that expression of a mutant cadherin-11 lacking the cytoplasmic juxtamembrane domain (JMD) diminished the turnover of α-catenin at adherens junctions as measured by fluorescence recovery after photobleaching. This resulted in markedly diminished cell intercalation into monolayers reflecting reduced cadherin-11-dependent cell motility on other cells. Furthermore, the actin cytoskeleton in cadherin-11 ΔJMD cells revealed a more extensive cortical F-actin ring that correlated with significantly higher levels of activated Rac1. Together, these studies implicate the cadherin-11 cytoplasmic JMD as a regulator of intercellular motility and cellular rearrangement in multicellular clusters and provide insight into a critical pathway that determines the behavior of fibroblast-like synoviocytes in arthritis, especially rheumatoid arthritis.