Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1983 Jul 1;97(1):145–152. doi: 10.1083/jcb.97.1.145

Neural cell adhesion molecule mediates initial interactions between spinal cord neurons and muscle cells in culture

PMCID: PMC2112489  PMID: 6863388

Abstract

Previous studies in this laboratory have described a cell surface glycoprotein, called neural cell adhesion molecule or N-CAM, that appears to be a ligand in the adhesion between neural membranes. N-CAM antigenic determinants were also shown to be present on embryonic muscle and an N-CAM-dependent adhesion was demonstrated between retinal cell membranes and muscle cells in short-term assays. The present studies indicate that these antigenic determinants are associated with the N-CAM polypeptide, and that rapid adhesion mediated by this molecule occurs between spinal cord membranes and muscle cells. Detailed examination of the effects of anti-(N-CAM) Fab' fragments in cultures of spinal cord with skeletal muscle showed that the Fab' fragments specifically block adhesion of spinal cord neurites and cells to myotubes. The Fab' did not affect binding of neurites to fibroblasts and collagen substrate, and did not alter myotube morphology. These results indicate that N-CAM adhesion is essential for the in vitro establishment of physical associations between nerve and muscle, and suggest that binding involving N-CAM may be an important early step in synaptogenesis.

Full Text

The Full Text of this article is available as a PDF (3.2 MB).

Selected References

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

  1. Bentley D., Keshishian H. Pathfinding by peripheral pioneer neurons in grasshoppers. Science. 1982 Dec 10;218(4577):1082–1088. doi: 10.1126/science.218.4577.1082. [DOI] [PubMed] [Google Scholar]
  2. Brackenbury R., Thiery J. P., Rutishauser U., Edelman G. M. Adhesion among neural cells of the chick embryo. I. An immunological assay for molecules involved in cell-cell binding. J Biol Chem. 1977 Oct 10;252(19):6835–6840. [PubMed] [Google Scholar]
  3. Buskirk D. R., Thiery J. P., Rutishauser U., Edelman G. M. Antibodies to a neural cell adhesion molecule disrupt histogenesis in cultured chick retinae. Nature. 1980 Jun 12;285(5765):488–489. doi: 10.1038/285488a0. [DOI] [PubMed] [Google Scholar]
  4. Christian C. N., Daniels M. P., Sugiyama H., Vogel Z., Jacques L., Nelson P. G. A factor from neurons increases the number of acetylcholine receptor aggregates on cultured muscle cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4011–4015. doi: 10.1073/pnas.75.8.4011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christian C. N., Nelson P. G., Peacock J., Nirenberg M. Synapse formation between two clonal cell lines. Science. 1977 May 27;196(4293):995–998. doi: 10.1126/science.193191. [DOI] [PubMed] [Google Scholar]
  6. Chuong C. M., McClain D. A., Streit P., Edelman G. M. Neural cell adhesion molecules in rodent brains isolated by monoclonal antibodies with cross-species reactivity. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4234–4238. doi: 10.1073/pnas.79.13.4234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cunningham B. A., Hoffman S., Rutishauser U., Hemperly J. J., Edelman G. M. Molecular topography of the neural cell adhesion molecule N-CAM: surface orientation and location of sialic acid-rich and binding regions. Proc Natl Acad Sci U S A. 1983 May;80(10):3116–3120. doi: 10.1073/pnas.80.10.3116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dennis M. J. Development of the neuromuscular junction: inductive interactions between cells. Annu Rev Neurosci. 1981;4:43–68. doi: 10.1146/annurev.ne.04.030181.000355. [DOI] [PubMed] [Google Scholar]
  9. Edelman G. M. Cell adhesion molecules. Science. 1983 Feb 4;219(4584):450–457. doi: 10.1126/science.6823544. [DOI] [PubMed] [Google Scholar]
  10. Edelman G. M., Chuong C. M. Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Proc Natl Acad Sci U S A. 1982 Nov;79(22):7036–7040. doi: 10.1073/pnas.79.22.7036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fambrough D. M. Control of acetylcholine receptors in skeletal muscle. Physiol Rev. 1979 Jan;59(1):165–227. doi: 10.1152/physrev.1979.59.1.165. [DOI] [PubMed] [Google Scholar]
  12. Fischbach G. D., Berg D. K., Cohen S. A., Frank E. Enrichment of nerve--muscle synapses in spinal cord--muscle cultures and identification of relative peaks of ACh sensitivity at sites of transmitter release. Cold Spring Harb Symp Quant Biol. 1976;40:347–357. doi: 10.1101/sqb.1976.040.01.034. [DOI] [PubMed] [Google Scholar]
  13. Grumet M., Rutishauser U., Edelman G. M. Neural cell adhesion molecule is on embryonic muscle cells and mediates adhesion to nerve cells in vitro. Nature. 1982 Feb 25;295(5851):693–695. doi: 10.1038/295693a0. [DOI] [PubMed] [Google Scholar]
  14. Henderson C. E., Huchet M., Changeux J. P. Neurite outgrowth from embryonic chicken spinal neurons is promoted by media conditioned by muscle cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2625–2629. doi: 10.1073/pnas.78.4.2625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ho R. K., Goodman C. S. Peripheral pathways are pioneered by an array of central and peripheral neurones in grasshopper embryos. Nature. 1982 Jun 3;297(5865):404–406. doi: 10.1038/297404a0. [DOI] [PubMed] [Google Scholar]
  16. Hoffman S., Sorkin B. C., White P. C., Brackenbury R., Mailhammer R., Rutishauser U., Cunningham B. A., Edelman G. M. Chemical characterization of a neural cell adhesion molecule purified from embryonic brain membranes. J Biol Chem. 1982 Jul 10;257(13):7720–7729. [PubMed] [Google Scholar]
  17. Jessell T. M., Siegel R. E., Fischbach G. D. Induction of acetylcholine receptors on cultured skeletal muscle by a factor extracted from brain and spinal cord. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5397–5401. doi: 10.1073/pnas.76.10.5397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kidokoro Y., Heinemann S., Schubert D., Brandt B. L., Klier F. G. Synapse formation and neurotrophic effects on muscle cell lines. Cold Spring Harb Symp Quant Biol. 1976;40:373–388. doi: 10.1101/sqb.1976.040.01.036. [DOI] [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Landmesser L. T. The generation of neuromuscular specificity. Annu Rev Neurosci. 1980;3:279–302. doi: 10.1146/annurev.ne.03.030180.001431. [DOI] [PubMed] [Google Scholar]
  21. McClain D. A., Edelman G. M. A neural cell adhesion molecule from human brain. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6380–6384. doi: 10.1073/pnas.79.20.6380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nelson P., Christian C., Nirenberg M. Synapse formation between clonal neuroblastoma X glioma hybrid cells and striated muscle cells. Proc Natl Acad Sci U S A. 1976 Jan;73(1):123–127. doi: 10.1073/pnas.73.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nurse C. A., O'Lague P. H. Formation of cholinergic synapses between dissociated sympathetic neurons and skeletal myotubes of the rat in cell culture. Proc Natl Acad Sci U S A. 1975 May;72(5):1955–1959. doi: 10.1073/pnas.72.5.1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Podleski T. R., Axelrod D., Ravdin P., Greenberg I., Johnson M. M., Salpeter M. M. Nerve extract induces increase and redistribution of acetylcholine receptors on cloned muscle cells. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2035–2039. doi: 10.1073/pnas.75.4.2035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Puro D. G., De Mello F. G., Nirenberg M. Synapse turnover: the formation and termination of transient synapses. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4977–4981. doi: 10.1073/pnas.74.11.4977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Puro D. G., Nirenberg M. On the specificity of synapse formation. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3544–3548. doi: 10.1073/pnas.73.10.3544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rothbard J. B., Brackenbury R., Cunningham B. A., Edelman G. M. Differences in the carbohydrate structures of neural cell-adhesion molecules from adult and embryonic chicken brains. J Biol Chem. 1982 Sep 25;257(18):11064–11069. [PubMed] [Google Scholar]
  28. Rutishauser U., Edelman G. M. Effects of fasciculation on the outgrowth of neurites from spinal ganglia in culture. J Cell Biol. 1980 Nov;87(2 Pt 1):370–378. doi: 10.1083/jcb.87.2.370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rutishauser U., Gall W. E., Edelman G. M. Adhesion among neural cells of the chick embryo. IV. Role of the cell surface molecule CAM in the formation of neurite bundles in cultures of spinal ganglia. J Cell Biol. 1978 Nov;79(2 Pt 1):382–393. doi: 10.1083/jcb.79.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rutishauser U., Hoffman S., Edelman G. M. Binding properties of a cell adhesion molecule from neural tissue. Proc Natl Acad Sci U S A. 1982 Jan;79(2):685–689. doi: 10.1073/pnas.79.2.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rutishauser U., Thiery J. P., Brackenbury R., Edelman G. M. Adhesion among neural cells of the chick embryo. III. Relationship of the surface molecule CAM to cell adhesion and the development of histotypic patterns. J Cell Biol. 1978 Nov;79(2 Pt 1):371–381. doi: 10.1083/jcb.79.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schaffner A. E., Daniels M. P. Conditioned medium from cultures of embryonic neurons contains a high molecular weight factor which induces acetylcholine receptor aggregation on cultured myotubes. J Neurosci. 1982 May;2(5):623–632. doi: 10.1523/JNEUROSCI.02-05-00623.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thiery J. P., Brackenbury R., Rutishauser U., Edelman G. M. Adhesion among neural cells of the chick embryo. II. Purification and characterization of a cell adhesion molecule from neural retina. J Biol Chem. 1977 Oct 10;252(19):6841–6845. [PubMed] [Google Scholar]
  34. Thiery J. P., Duband J. L., Rutishauser U., Edelman G. M. Cell adhesion molecules in early chicken embryogenesis. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6737–6741. doi: 10.1073/pnas.79.21.6737. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES