Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1995 Apr 1;129(1):189–202. doi: 10.1083/jcb.129.1.189

Novel E-cadherin-mediated adhesion in peripheral nerve: Schwann cell architecture is stabilized by autotypic adherens junctions [published erratum appears in J Cell Biol 1995 Jun;129(6):1721]

PMCID: PMC2120363  PMID: 7698985

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.

Full Text

The Full Text of this article is available as a PDF (7.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bergoffen J., Scherer S. S., Wang S., Scott M. O., Bone L. J., Paul D. L., Chen K., Lensch M. W., Chance P. F., Fischbeck K. H. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science. 1993 Dec 24;262(5142):2039–2042. doi: 10.1126/science.8266101. [DOI] [PubMed] [Google Scholar]
  3. Berndorff D., Gessner R., Kreft B., Schnoy N., Lajous-Petter A. M., Loch N., Reutter W., Hortsch M., Tauber R. Liver-intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. J Cell Biol. 1994 Jun;125(6):1353–1369. doi: 10.1083/jcb.125.6.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blank W. F., Jr, Bunge M. B., Bunge R. P. The sensitivity of the myelin sheath, particularly the Schwann cell-axolemmal junction, to lowered calcium levels in cultured sensory ganglia. Brain Res. 1974 Mar 8;67(3):503–518. doi: 10.1016/0006-8993(74)90498-3. [DOI] [PubMed] [Google Scholar]
  5. Boller K., Vestweber D., Kemler R. Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol. 1985 Jan;100(1):327–332. doi: 10.1083/jcb.100.1.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bunge R. P., Bunge M. B., Bates M. Movements of the Schwann cell nucleus implicate progression of the inner (axon-related) Schwann cell process during myelination. J Cell Biol. 1989 Jul;109(1):273–284. doi: 10.1083/jcb.109.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. D'Urso D., Brophy P. J., Staugaitis S. M., Gillespie C. S., Frey A. B., Stempak J. G., Colman D. R. Protein zero of peripheral nerve myelin: biosynthesis, membrane insertion, and evidence for homotypic interaction. Neuron. 1990 Mar;4(3):449–460. doi: 10.1016/0896-6273(90)90057-m. [DOI] [PubMed] [Google Scholar]
  8. Doyle J. P., Colman D. R. Glial-neuron interactions and the regulation of myelin formation. Curr Opin Cell Biol. 1993 Oct;5(5):779–785. doi: 10.1016/0955-0674(93)90025-l. [DOI] [PubMed] [Google Scholar]
  9. Einheber S., Milner T. A., Giancotti F., Salzer J. L. Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination. J Cell Biol. 1993 Dec;123(5):1223–1236. doi: 10.1083/jcb.123.5.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Filbin M. T., Walsh F. S., Trapp B. D., Pizzey J. A., Tennekoon G. I. Role of myelin P0 protein as a homophilic adhesion molecule. Nature. 1990 Apr 26;344(6269):871–872. doi: 10.1038/344871a0. [DOI] [PubMed] [Google Scholar]
  11. Fleming T. P., Johnson M. H. From egg to epithelium. Annu Rev Cell Biol. 1988;4:459–485. doi: 10.1146/annurev.cb.04.110188.002331. [DOI] [PubMed] [Google Scholar]
  12. Geiger B., Ayalon O. Cadherins. Annu Rev Cell Biol. 1992;8:307–332. doi: 10.1146/annurev.cb.08.110192.001515. [DOI] [PubMed] [Google Scholar]
  13. Geiger B., Ginsberg D. The cytoplasmic domain of adherens-type junctions. Cell Motil Cytoskeleton. 1991;20(1):1–6. doi: 10.1002/cm.970200102. [DOI] [PubMed] [Google Scholar]
  14. Ghabriel M. N., Allt G. Incisures of Schmidt-Lanterman. Prog Neurobiol. 1981;17(1-2):25–58. doi: 10.1016/0301-0082(81)90003-4. [DOI] [PubMed] [Google Scholar]
  15. Gillespie C. S., Sherman D. L., Blair G. E., Brophy P. J. Periaxin, a novel protein of myelinating Schwann cells with a possible role in axonal ensheathment. Neuron. 1994 Mar;12(3):497–508. doi: 10.1016/0896-6273(94)90208-9. [DOI] [PubMed] [Google Scholar]
  16. Gould R. M., Sinatra R. S. Internodal distribution of phosphatidylcholine biosynthetic activity in teased peripheral nerve fibres: an autoradiographic study. J Neurocytol. 1981 Apr;10(2):161–167. doi: 10.1007/BF01257964. [DOI] [PubMed] [Google Scholar]
  17. Griffiths I. R., Mitchell L. S., McPhilemy K., Morrison S., Kyriakides E., Barrie J. A. Expression of myelin protein genes in Schwann cells. J Neurocytol. 1989 Jun;18(3):345–352. doi: 10.1007/BF01190837. [DOI] [PubMed] [Google Scholar]
  18. Gumbiner B. M. Proteins associated with the cytoplasmic surface of adhesion molecules. Neuron. 1993 Oct;11(4):551–564. doi: 10.1016/0896-6273(93)90068-3. [DOI] [PubMed] [Google Scholar]
  19. Gumbiner B., Simons K. The role of uvomorulin in the formation of epithelial occluding junctions. Ciba Found Symp. 1987;125:168–186. doi: 10.1002/9780470513408.ch11. [DOI] [PubMed] [Google Scholar]
  20. Hall S. M., Williams P. L. Studies on the "incisures" of Schmidt and Lanterman. J Cell Sci. 1970 May;6(3):767–791. doi: 10.1242/jcs.6.3.767. [DOI] [PubMed] [Google Scholar]
  21. Hinck L., Näthke I. S., Papkoff J., Nelson W. J. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. doi: 10.1083/jcb.125.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hirano S., Kimoto N., Shimoyama Y., Hirohashi S., Takeichi M. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992 Jul 24;70(2):293–301. doi: 10.1016/0092-8674(92)90103-j. [DOI] [PubMed] [Google Scholar]
  23. Joe E. H., Angelides K. Clustering of voltage-dependent sodium channels on axons depends on Schwann cell contact. Nature. 1992 Mar 26;356(6367):333–335. doi: 10.1038/356333a0. [DOI] [PubMed] [Google Scholar]
  24. Kintner C. Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain. Cell. 1992 Apr 17;69(2):225–236. doi: 10.1016/0092-8674(92)90404-z. [DOI] [PubMed] [Google Scholar]
  25. Kordeli E., Davis J., Trapp B., Bennett V. An isoform of ankyrin is localized at nodes of Ranvier in myelinated axons of central and peripheral nerves. J Cell Biol. 1990 Apr;110(4):1341–1352. doi: 10.1083/jcb.110.4.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Le Bivic A., Sambuy Y., Mostov K., Rodriguez-Boulan E. Vectorial targeting of an endogenous apical membrane sialoglycoprotein and uvomorulin in MDCK cells. J Cell Biol. 1990 May;110(5):1533–1539. doi: 10.1083/jcb.110.5.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lee V. M., Carden M. J., Schlaepfer W. W., Trojanowski J. Q. Monoclonal antibodies distinguish several differentially phosphorylated states of the two largest rat neurofilament subunits (NF-H and NF-M) and demonstrate their existence in the normal nervous system of adult rats. J Neurosci. 1987 Nov;7(11):3474–3488. doi: 10.1523/JNEUROSCI.07-11-03474.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Magee A. I., Buxton R. S. Transmembrane molecular assemblies regulated by the greater cadherin family. Curr Opin Cell Biol. 1991 Oct;3(5):854–861. doi: 10.1016/0955-0674(91)90060-c. [DOI] [PubMed] [Google Scholar]
  29. Mugnaini E., Schnapp B. Possible role of zonula occludens of the myelin sheath in demyelinating conditions. Nature. 1974 Oct 25;251(5477):725–727. doi: 10.1038/251725a0. [DOI] [PubMed] [Google Scholar]
  30. Nagafuchi A., Shirayoshi Y., Okazaki K., Yasuda K., Takeichi M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature. 1987 Sep 24;329(6137):341–343. doi: 10.1038/329341a0. [DOI] [PubMed] [Google Scholar]
  31. Nagafuchi A., Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988 Dec 1;7(12):3679–3684. doi: 10.1002/j.1460-2075.1988.tb03249.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nusse R., Varmus H. E. Wnt genes. Cell. 1992 Jun 26;69(7):1073–1087. doi: 10.1016/0092-8674(92)90630-u. [DOI] [PubMed] [Google Scholar]
  33. Näthke I. S., Hinck L., Swedlow J. R., Papkoff J., Nelson W. J. Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells. J Cell Biol. 1994 Jun;125(6):1341–1352. doi: 10.1083/jcb.125.6.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Peifer M. The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction. J Cell Sci. 1993 Aug;105(Pt 4):993–1000. doi: 10.1242/jcs.105.4.993. [DOI] [PubMed] [Google Scholar]
  36. Rosenbluth J. Role of glial cells in the differentiation and function of myelinated axons. Int J Dev Neurosci. 1988;6(1):3–24. doi: 10.1016/0736-5748(88)90025-1. [DOI] [PubMed] [Google Scholar]
  37. Shimamura K., Takahashi T., Takeichi M. E-cadherin expression in a particular subset of sensory neurons. Dev Biol. 1992 Aug;152(2):242–254. doi: 10.1016/0012-1606(92)90132-z. [DOI] [PubMed] [Google Scholar]
  38. Shirayoshi Y., Nose A., Iwasaki K., Takeichi M. N-linked oligosaccharides are not involved in the function of a cell-cell binding glycoprotein E-cadherin. Cell Struct Funct. 1986 Sep;11(3):245–252. doi: 10.1247/csf.11.245. [DOI] [PubMed] [Google Scholar]
  39. Singer M., Bryant S. V. Movements in the myelin Schwann sheath of the vertebrate axon. Nature. 1969 Mar 22;221(5186):1148–1150. doi: 10.1038/2211148a0. [DOI] [PubMed] [Google Scholar]
  40. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
  41. Trapp B. D., Andrews S. B., Wong A., O'Connell M., Griffin J. W. Co-localization of the myelin-associated glycoprotein and the microfilament components, F-actin and spectrin, in Schwann cells of myelinated nerve fibres. J Neurocytol. 1989 Feb;18(1):47–60. doi: 10.1007/BF01188423. [DOI] [PubMed] [Google Scholar]
  42. Uchiyama N., Hasegawa M., Yamashima T., Yamashita J., Shimamura K., Takeichi M. Immunoelectron microscopic localization of E-cadherin in dorsal root ganglia, dorsal root and dorsal horn of postnatal mice. J Neurocytol. 1994 Aug;23(8):460–468. doi: 10.1007/BF01184070. [DOI] [PubMed] [Google Scholar]
  43. Volk T., Geiger B. A-CAM: a 135-kD receptor of intercellular adherens junctions. I. Immunoelectron microscopic localization and biochemical studies. J Cell Biol. 1986 Oct;103(4):1441–1450. doi: 10.1083/jcb.103.4.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Volk T., Geiger B. A-CAM: a 135-kD receptor of intercellular adherens junctions. II. Antibody-mediated modulation of junction formation. J Cell Biol. 1986 Oct;103(4):1451–1464. doi: 10.1083/jcb.103.4.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wheelock M. J., Jensen P. J. Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin. J Cell Biol. 1992 Apr;117(2):415–425. doi: 10.1083/jcb.117.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES