NOVEL E-CADHERIN-MEDIATED ADHESION IN PERIPHERAL-NERVE - SCHWANN-CELLARCHITECTURE IS STABILIZED BY AUTOTYPIC ADHERENS JUNCTIONS

Previous studies (Blank, W. F., M. B. Bunge, and R. P. Bunge. 1974. Br ain Res. 67:503-518) showed that Schwann cell paranodal membranes were disrupted in calcium free medium suggesting that cadherin mediated me chanisms may operate to maintain the integrity of the paranodal membra ne complex. Using antibodies against the fifth extracellular domain of E-cadherin, we now show by confocal laser and electron immunomicrosco py that E-cadherin is a major adhesive glycoprotein in peripheral nerv ous system Schwann cells. E-Cadherin is not found, however, in compact myelin bilayers. Rather, it is concentrated at the paranodes, in Schm idt-Lanterman incisures, and at the inner and outer loops. At these lo ci, E-cadherin is associated with subplasmalemmal electron densities t hat coordinate in register across several cytoplasmic turns of a singl e Schwann cell. F-Actin and beta-catenin, two proteins implicated in c ellular signaling, also co-localize to E-cadherin positive sites. Thes e 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 cell s and the axon. Our findings demonstrate that E-cadherin and its assoc iated proteins are essential components in the architecture of the Sch wann cell cytoplasmic channel network, and suggest that this network h as specialized functions in addition to those required for myelinogene sis.