Novel E-cadherin-mediated adhesion in peripheral nerve: Schwann cell architecture is stabilized by autotypic adherens junctions.

Abstract

Previous studies (Blank, W. F., M. B. Bunge, and R. P. Bunge. 1974. Brain Res. 67:503-518) showed that Schwann cell paranodal membranes were disrupted in calcium free medium suggesting that cadherin mediated mechanisms may operate to maintain the integrity of the paranodal membrane complex. Using antibodies against the fifth extracellular domain of E-cadherin, we now show by confocal laser and electron immunomicroscopy that E-cadherin is a major adhesive glycoprotein in peripheral nervous system Schwann cells. E-Cadherin is not found, however, in compact myelin bilayers. Rather, it is concentrated at the paranodes, in Schmidt-Lanterman incisures, and at the inner and outer loops. At these loci, E-cadherin is associated with subplasmalemmal electron densities that coordinate in register across several cytoplasmic turns of a single Schwann cell. F-Actin and beta-catenin, two proteins implicated in cellular signaling, also co-localize to E-cadherin positive sites. These complexes are autotypic adherens-type junctions that are confined to the plasma membrane synthesized by a single Schwann cell; E-cadherin was never observed between two Schwann cells, nor between Schwann cells and the axon. Our findings demonstrate that E-cadherin and its associated proteins are essential components in the architecture of the Schwann cell cytoplasmic channel network, and suggest that this network has specialized functions in addition to those required for myelinogenesis.