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. 1996 Nov 1;135(3):767–779. doi: 10.1083/jcb.135.3.767

The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones

PMCID: PMC2121068  PMID: 8909549

Abstract

Molecular mechanisms linking pre- and postsynaptic membranes at the interneuronal synapses are little known. We tested the cadherin adhesion system for its localization in synapses of mouse and chick brains. We found that two classes of cadherin-associated proteins, alpha N- and beta-catenin, are broadly distributed in adult brains, colocalizing with a synaptic marker, synaptophysin. At the ultrastructural level, these proteins were localized in synaptic junctions of various types, forming a symmetrical adhesion structure. These structures sharply bordered the transmitter release sites associated with synaptic vesicles, although their segregation was less clear in certain types of synapses. N-cadherin was also localized at a similar site of synaptic junctions but in restricted brain nuclei. In developing synapses, the catenin-bearing contacts dominated their junctional structures. These findings demonstrate that interneuronal synaptic junctions comprise two subdomains, transmitter release zone and catenin-based adherens junction. The catenins localized in these junctions are likely associated with certain cadherin molecules including N-cadherin, and the cadherin/ catenin complex may play a critical role in the formation or maintenance of synaptic junctions.

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Selected References

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  1. Aberle H., Butz S., Stappert J., Weissig H., Kemler R., Hoschuetzky H. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J Cell Sci. 1994 Dec;107(Pt 12):3655–3663. doi: 10.1242/jcs.107.12.3655. [DOI] [PubMed] [Google Scholar]
  2. Adinolfi A. M. Morphogenesis of synaptic junctions in layers I and II of the somatic sensory cortex. Exp Neurol. 1972 Mar;34(3):372–382. doi: 10.1016/0014-4886(72)90035-0. [DOI] [PubMed] [Google Scholar]
  3. Altman J. Postnatal development of the cerebellar cortex in the rat. 3. Maturation of the components of the granular layer. J Comp Neurol. 1972 Aug;145(4):465–513. doi: 10.1002/cne.901450403. [DOI] [PubMed] [Google Scholar]
  4. Beesley P. W., Mummery R., Tibaldi J. N-cadherin is a major glycoprotein component of isolated rat forebrain postsynaptic densities. J Neurochem. 1995 May;64(5):2288–2294. doi: 10.1046/j.1471-4159.1995.64052288.x. [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. Burry R. W., Vandré D. D., Hayes D. M. Silver enhancement of gold antibody probes in pre-embedding electron microscopic immunocytochemistry. J Histochem Cytochem. 1992 Dec;40(12):1849–1856. doi: 10.1177/40.12.1453003. [DOI] [PubMed] [Google Scholar]
  7. Chang H. T., Kita H., Kitai S. T. The fine structure of the rat subthalamic nucleus: an electron microscopic study. J Comp Neurol. 1983 Nov 20;221(1):113–123. doi: 10.1002/cne.902210110. [DOI] [PubMed] [Google Scholar]
  8. Colonnier M. Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscope study. Brain Res. 1968 Jul;9(2):268–287. doi: 10.1016/0006-8993(68)90234-5. [DOI] [PubMed] [Google Scholar]
  9. Fannon A. M., Sherman D. L., Ilyina-Gragerova G., Brophy P. J., Friedrich V. L., Jr, Colman D. R. Novel E-cadherin-mediated adhesion in peripheral nerve: Schwann cell architecture is stabilized by autotypic adherens junctions. J Cell Biol. 1995 Apr;129(1):189–202. doi: 10.1083/jcb.129.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GRAY E. G. Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study. J Anat. 1959 Oct;93:420–433. [PMC free article] [PubMed] [Google Scholar]
  11. Gautam M., Noakes P. G., Moscoso L., Rupp F., Scheller R. H., Merlie J. P., Sanes J. R. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell. 1996 May 17;85(4):525–535. doi: 10.1016/s0092-8674(00)81253-2. [DOI] [PubMed] [Google Scholar]
  12. Gray E. G., Hamlyn L. H. Electron microscopy of experimental degeneration in the avian optic tectum. J Anat. 1962 Jul;96(Pt 3):309–316.5. [PMC free article] [PubMed] [Google Scholar]
  13. Gumbiner B., Simons K. A functional assay for proteins involved in establishing an epithelial occluding barrier: identification of a uvomorulin-like polypeptide. J Cell Biol. 1986 Feb;102(2):457–468. doi: 10.1083/jcb.102.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gumbiner B., Stevenson B., Grimaldi A. The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol. 1988 Oct;107(4):1575–1587. doi: 10.1083/jcb.107.4.1575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hall Z. W., Sanes J. R. Synaptic structure and development: the neuromuscular junction. Cell. 1993 Jan;72 (Suppl):99–121. doi: 10.1016/s0092-8674(05)80031-5. [DOI] [PubMed] [Google Scholar]
  16. Hatta K., Takeichi M. Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature. 1986 Apr 3;320(6061):447–449. doi: 10.1038/320447a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Hirano S., Takeichi M. Differential expression of alpha N-catenin and N-cadherin during early development of chicken embryos. Int J Dev Biol. 1994 Jun;38(2):379–384. [PubMed] [Google Scholar]
  19. Hunt S. P., Künzle H. Observations on the projections and intrinsic organization of the pigeon optic tectum: an autoradiographic study based on anterograde and retrograde, axonal and dendritic flow. J Comp Neurol. 1976 Nov 15;170(2):153–172. doi: 10.1002/cne.901700203. [DOI] [PubMed] [Google Scholar]
  20. Ilinsky I. A., Kultas-Ilinsky K. Fine structure of the magnocellular subdivision of the ventral anterior thalamic nucleus (VAmc) of Macaca mulatta: I. Cell types and synaptology. J Comp Neurol. 1990 Apr 15;294(3):455–478. doi: 10.1002/cne.902940313. [DOI] [PubMed] [Google Scholar]
  21. Jessell T. M., Kandel E. R. Synaptic transmission: a bidirectional and self-modifiable form of cell-cell communication. Cell. 1993 Jan;72 (Suppl):1–30. doi: 10.1016/s0092-8674(05)80025-x. [DOI] [PubMed] [Google Scholar]
  22. Jongens T. A., Ackerman L. D., Swedlow J. R., Jan L. Y., Jan Y. N. Germ cell-less encodes a cell type-specific nuclear pore-associated protein and functions early in the germ-cell specification pathway of Drosophila. Genes Dev. 1994 Sep 15;8(18):2123–2136. doi: 10.1101/gad.8.18.2123. [DOI] [PubMed] [Google Scholar]
  23. Jou T. S., Stewart D. B., Stappert J., Nelson W. J., Marrs J. A. Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex. Proc Natl Acad Sci U S A. 1995 May 23;92(11):5067–5071. doi: 10.1073/pnas.92.11.5067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993 Sep;9(9):317–321. doi: 10.1016/0168-9525(93)90250-l. [DOI] [PubMed] [Google Scholar]
  25. Matsumine A., Ogai A., Senda T., Okumura N., Satoh K., Baeg G. H., Kawahara T., Kobayashi S., Okada M., Toyoshima K. Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein. Science. 1996 May 17;272(5264):1020–1023. doi: 10.1126/science.272.5264.1020. [DOI] [PubMed] [Google Scholar]
  26. Meyer R. A., Laird D. W., Revel J. P., Johnson R. G. Inhibition of gap junction and adherens junction assembly by connexin and A-CAM antibodies. J Cell Biol. 1992 Oct;119(1):179–189. doi: 10.1083/jcb.119.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nakagawa S., Takeichi M. Neural crest cell-cell adhesion controlled by sequential and subpopulation-specific expression of novel cadherins. Development. 1995 May;121(5):1321–1332. doi: 10.1242/dev.121.5.1321. [DOI] [PubMed] [Google Scholar]
  28. Navone F., Jahn R., Di Gioia G., Stukenbrok H., Greengard P., De Camilli P. Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J Cell Biol. 1986 Dec;103(6 Pt 1):2511–2527. doi: 10.1083/jcb.103.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Noakes P. G., Gautam M., Mudd J., Sanes J. R., Merlie J. P. Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2. Nature. 1995 Mar 16;374(6519):258–262. doi: 10.1038/374258a0. [DOI] [PubMed] [Google Scholar]
  30. Oda H., Uemura T., Harada Y., Iwai Y., Takeichi M. A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev Biol. 1994 Oct;165(2):716–726. doi: 10.1006/dbio.1994.1287. [DOI] [PubMed] [Google Scholar]
  31. Peters A., Sethares C., Harriman K. M. Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. II. Synaptic junctions. J Neurocytol. 1990 Aug;19(4):584–600. doi: 10.1007/BF01257246. [DOI] [PubMed] [Google Scholar]
  32. Redies C. Cadherin expression in the developing vertebrate CNS: from neuromeres to brain nuclei and neural circuits. Exp Cell Res. 1995 Oct;220(2):243–256. doi: 10.1006/excr.1995.1313. [DOI] [PubMed] [Google Scholar]
  33. Redies C., Engelhart K., Takeichi M. Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain. J Comp Neurol. 1993 Jul 15;333(3):398–416. doi: 10.1002/cne.903330307. [DOI] [PubMed] [Google Scholar]
  34. Rose O., Grund C., Reinhardt S., Starzinski-Powitz A., Franke W. W. Contactus adherens, a special type of plaque-bearing adhering junction containing M-cadherin, in the granule cell layer of the cerebellar glomerulus. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6022–6026. doi: 10.1073/pnas.92.13.6022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rubinfeld B., Souza B., Albert I., Müller O., Chamberlain S. H., Masiarz F. R., Munemitsu S., Polakis P. Association of the APC gene product with beta-catenin. Science. 1993 Dec 10;262(5140):1731–1734. doi: 10.1126/science.8259518. [DOI] [PubMed] [Google Scholar]
  36. Shibamoto S., Hayakawa M., Takeuchi K., Hori T., Miyazawa K., Kitamura N., Johnson K. R., Wheelock M. J., Matsuyoshi N., Takeichi M. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J Cell Biol. 1995 Mar;128(5):949–957. doi: 10.1083/jcb.128.5.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shimamura K., Hirano S., McMahon A. P., Takeichi M. Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain. Development. 1994 Aug;120(8):2225–2234. doi: 10.1242/dev.120.8.2225. [DOI] [PubMed] [Google Scholar]
  38. Spacek J., Lieberman A. R. Ultrastructure and three-dimensional organization of synaptic glomeruli in rat somatosensory thalamus. J Anat. 1974 Jul;117(Pt 3):487–516. [PMC free article] [PubMed] [Google Scholar]
  39. Su L. K., Vogelstein B., Kinzler K. W. Association of the APC tumor suppressor protein with catenins. Science. 1993 Dec 10;262(5140):1734–1737. doi: 10.1126/science.8259519. [DOI] [PubMed] [Google Scholar]
  40. Takeichi M. Morphogenetic roles of classic cadherins. Curr Opin Cell Biol. 1995 Oct;7(5):619–627. doi: 10.1016/0955-0674(95)80102-2. [DOI] [PubMed] [Google Scholar]
  41. Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988 Apr;102(4):639–655. doi: 10.1242/dev.102.4.639. [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. Vaughn J. E. Fine structure of synaptogenesis in the vertebrate central nervous system. Synapse. 1989;3(3):255–285. doi: 10.1002/syn.890030312. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Watabe M., Nagafuchi A., Tsukita S., Takeichi M. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J Cell Biol. 1994 Oct;127(1):247–256. doi: 10.1083/jcb.127.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wouterlood F. G., Mugnaini E., Osen K. K., Dahl A. L. Stellate neurons in rat dorsal cochlear nucleus studies with combined Golgi impregnation and electron microscopy: synaptic connections and mutual coupling by gap junctions. J Neurocytol. 1984 Aug;13(4):639–664. doi: 10.1007/BF01148083. [DOI] [PubMed] [Google Scholar]
  47. Yamagata M., Herman J. P., Sanes J. R. Lamina-specific expression of adhesion molecules in developing chick optic tectum. J Neurosci. 1995 Jun;15(6):4556–4571. doi: 10.1523/JNEUROSCI.15-06-04556.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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