E-cadherin is required for the correct formation of autotypic adherens junctions of the outer mesaxon but not for the integrity of myelinated fibers of peripheral nerves.
The calcium-dependent adhesion protein E-cadherin is present in noncompacted regions of myelin sheaths in the peripheral nervous system. There, it is localized to electron-dense structures between membranes of the same Schwann cell referred to as autotypic adherens junctions. It has been suggested that the failure of E-cadherin-mediated adhesion might cause demyelination that proceeds in certain pathological states. To test the requirement of E-cadherin in peripheral nerves, we used tissue-specific gene ablation techniques based on the Cre/LoxP system. We show that E-cadherin deficiency does not cause significant demyelination up to the age of 15 months. Immunostainings for nodal sodium channels, the paranodal protein Caspr1, and the juxtaparanodal potassium channels Kv1.1 and Kv1.2 revealed that E-cadherin is not necessary to maintain the general functional architecture of the nodal region. On the ultrastructural level, we detected a widening of the outer mesaxon accompanied by a loss of electron-dense cytoplasmic areas. We conclude that E-cadherin is required for the proper establishment and/or the maintenance of the outer mesaxon in myelinated PNS fibers but is dispensable for proper nerve function.
Young
Peter
P
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, CH-8093 Zürich, Switzerland.
Boussadia
Oreda
O
Berger
Philipp
P
Leone
Dino P
DP
Charnay
Patrick
P
Kemler
Rolf
R
Suter
Ueli
U
D022005:Adherens Junctions / Q000378:metabolism* / Q000648:ultrastructure*; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure*; D010525:Peripheral Nerves / Q000378:metabolism* / Q000648:ultrastructure; D012583:Schwann Cells / Q000378:metabolism / Q000648:ultrastructure
D015820:Cadherins