Biallelic mutations in the neurofibromatosis 2 (NF2) gene are linked to 
schwannoma and meningioma tumorigenesis. Cells with NF2 mutations exhibit 
elevated levels of phosphorylated extracellular signal-regulated kinase (ERK) 
and aberrant cell-cell and cell-matrix contacts. The NF2 gene product, merlin, 
associates with adherens junction protein complexes, suggesting that part of its 
function as a tumor suppressor involves regulating cell junctions. Here, we find 
that a novel PDZ protein, called erbin, binds directly to the merlin-binding 
partner, EBP0, and regulates adherens junction dissociation through a MAP 
kinase-dependent mechanism. Reducing erbin expression using a targeted siRNA in 
primary cultures of Schwann cells results in altered cell-cell interactions, 
disruption of E-cadherin adherens junctions, increased cell proliferation, and 
elevated levels of phosphorylated ERK, all phenotypes observed in cells that 
lack merlin. Reduction of erbin expression also results in the dissociation of 
merlin from adherens junction proteins and an increase in the levels of 
phosphorylated merlin. These phenotypes can be rescued if cells with reduced 
levels of erbin are treated with a pharmacological inhibitor of ERK kinase. 
Collectively, these data indicate that erbin regulates MAP kinase activation in 
Schwann cells and suggest that erbin links merlin to both adherens junction 
protein complexes and the MAP kinase signaling pathway.