E-CADHERIN AND β-CATENIN COMPLEX IN ANIMAL MODELS OF HEREDITARY DEMYELINATING PERIPHERAL NEUROPATHY

E-cadherin, a major adhesive glycoprotein in Schwann cells (Fannon et al., 1995), is localized at the paranode, at Schmidt-Lanterman incisures in the peripheral nerve along with β-catenin, and associated with adherens-type junctions. To investigate the functional role of E-cadherin/β-catenin complex in Schwann cells biology, we studied expression and localization of E-cadherin and β-catenin complex in sciatic nerve from normal mice and from animal model of hereditary demyelinating peripheral neuropathy. We found that E-cadherin mRNA and proteins levels are regulated in normal mouse sciatic nerve during development like other myelin proteins. Furthermore, E-cadherin expression in regenerating nerve is mediated by axonal/SC interaction. On the contrary, β-catenin mRNA and protein levels did not change during development and following nerve lesion. Moreover, E-cadherin/β-catenin complex localization is altered in P0 knockout mice (P0-/-). In fact, E-cadherin was diffusely distributed throughout the fibers in an unusual beaded pattern of staining, and β-catenin was found in the perinuclear region of P0 -/- Schwann cells. Furthermore, E-cadherin/β-catenin complex localization is altered in peripheral nerve from other model of primary demielination where myelin compaction is lacking, such as Trembler-J mice, while it is normally localized in Trembler mice, where demyelination is less severe and compaction is preserved. In conclusion, it appears that the process that leads to a restricted localization of E-cadherin at the paranodal region is highly regulated and is disrupted in the peripheral nerve lacking compaction. Therefore, compaction contributes to the process of reorganization of the Schwann cells membrane during myelination and formation of a mature paranode. Altered E-cadherin/β-catenin complex localization, associated with absence of adherens junctions lead to changes in the structure of the paranodal region with important consequences on the molecular architecture of the Node of Ranvier, which lead to an altered transmission of impulses along axons, having important consequences in the pathogenesis of hereditary demyelinating peripheral neuropathy.