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Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice

Abstract

OF numerous synaptic components that have been identified, perhaps the best-studied are the nicotinic acetylcholine receptors (AChRs) of the vertebrate neuromuscular junction1. AChRs are diffusely distributed on embryonic myotubes, but become highly concentrated (~ 10,000 µm-2) in the postsynaptic membrane as development proceeds. At least two distinct processes contribute to this accumulation. One is local synthesis: subsynaptic muscle nuclei transcribe AChR subunit genes at higher rates than extra-synaptic nuclei, so AChR messenger RNA is concentrated near synaptic sites2,3. Second, once AChRs have been inserted in the membrane, they form high-density clusters by tethering to a sub-synaptic cytoskeletal complex. A key component of this complex is rapsyn, a peripheral membrane protein of relative molecular mass 43K (refs 4, 5), which is precisely colocalized with AChRs at synaptic sites from the earliest stages of neuromuscular synaptogenesis6. In heterologous systems, expression of recombi-nant rapsyn leads to clustering of diffusely distributed AChRs, suggesting that rapsyn may control formation of clusters7,8. To assess the role of rapsyn in vivo, we generated and characterized mutant mice with a targeted disruption of the Rapsn gene. We report that rapsyn is essential for the formation of AChR clusters, but that synapse-specific transcription of AChR subunit genes can proceed in its absence.

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References

  1. Hall, Z. W. & Sanes, J. R. Cell 72/Neuron 10 (suppl.) 99–121 (1993).

    Article  PubMed  Google Scholar 

  2. Merlie, J. P. & Sanes, J. R. Nature 317, 66–68 (1985).

    ADS  CAS  Article  PubMed  Google Scholar 

  3. Chu, G. C., Velleca, M. A. & Merlie, J. P. Sem. dev. Biol. 6, 175–183 (1995).

    CAS  Article  Google Scholar 

  4. Neubig, R. R., Krodel, E. K., Boyd, N. D. & Cohen, J. B. Proc. natn. Acad. Sci. U.S.A. 76, 690–694 (1979).

    ADS  CAS  Article  Google Scholar 

  5. Frail, D. E., McLaughlin, L. L., Mudd, J. & Merlie, J. P. J. biol. Chem. 263, 15602–15607 (1988).

    CAS  PubMed  Google Scholar 

  6. Noakes, P. G., Philips, W. D., Hanley, T. A., Sanes, J. R. & Merlie, J. P. Devl Biol. 155, 275–280 (1993).

    CAS  Article  Google Scholar 

  7. Froehner, S. C., Luetje, C. W., Scotland, P. B. & Patrick, J. Neuron 5, 403–410 (1990).

    CAS  Article  PubMed  Google Scholar 

  8. Phillips, W. D. et al. Science 251, 568–570 (1991).

    ADS  CAS  Article  PubMed  Google Scholar 

  9. Gautam, M. et al. Genomics 24, 366–369 (1994).

    CAS  Article  PubMed  Google Scholar 

  10. Musil, L. S., Frail, D. E. & Merlie J. P. J. Cell Biol. 108, 1833–1840 (1989).

    CAS  Article  PubMed  Google Scholar 

  11. Merlie, J. P., Heinemann, S. & Lindstrom, J. M. J. biol. Chem. 254, 6320–6327 (1979).

    CAS  PubMed  Google Scholar 

  12. Ferns, M., Campanelli, J. T., Hoch, W., Scheller, R. H. & Hall, Z. W. Neuron 11, 491–502 (1993).

    CAS  Article  PubMed  Google Scholar 

  13. Sanes, J. R. et al. Development 113, 1181–1191 (1991).

    CAS  PubMed  Google Scholar 

  14. Ervasti, J. M. & Campbell, K. P. Curr. Opin. Cell Biol. 5, 82–87 (1993).

    CAS  Article  PubMed  Google Scholar 

  15. Tinsley, J. M. et al. Nature 360, 591–593 (1992).

    ADS  CAS  Article  PubMed  Google Scholar 

  16. Yang, B., Ibraghimov-Beskrovnaya, O., Moomaw, C. R., Slaughter, C. A. & Campbell, K. P. J. biol. Chem. 269, 6040–6044 (1994).

    CAS  PubMed  Google Scholar 

  17. Yoshida, M. & Ozawa, E. J. Biochem, Tokyo 108, 748–752 (1990).

    CAS  Article  Google Scholar 

  18. Kramarcy, N. R., Vidal, A., Froehner, S. C. & Sealock, R. J. biol. Chem. 269, 2870–2876 (1994).

    CAS  PubMed  Google Scholar 

  19. Ibraghimov-Beskrovnaya, O. et al. Nature 355, 696–702 (1992).

    ADS  CAS  Article  PubMed  Google Scholar 

  20. Apel, E. D., Roberds, S. L. Campbell, K. P. & Merlie J. P. Neuron 15, 115–126 (1995).

    CAS  Article  PubMed  Google Scholar 

  21. Buckley, K. & Kelly, R. B. J. Cell Biol. 100, 1284–1294 (1985).

    CAS  Article  PubMed  Google Scholar 

  22. Sanes, J. R. Sem. dev. Biol. 6, 163–173 (1995).

    CAS  Article  Google Scholar 

  23. LaRochelle, W. J., Ralston, E., Forsayeth, J. R., Froehner, S. C. & Hall, Z. W. Devl Biol. 132, 130–138 (1989).

    CAS  Article  Google Scholar 

  24. Lupa, M. T. & Hall, Z. W. J. Neurosci. 9, 3937–3945 (1989).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).

    CAS  Article  PubMed  Google Scholar 

  26. Chu, G. C., Moscoso, L. M., Sliwkowski, M. X. & Merlie, J. P. Neuron 14, 329–339 (1995).

    CAS  Article  PubMed  Google Scholar 

  27. Moscoso, L. M., Merlie, J. P. & Sanes, J. R. Molec. cell. Neurosci. 6, 80–89 (1995).

    CAS  Article  PubMed  Google Scholar 

  28. Crowder, C. M. & Merlie, J. P. Molec. cell. Biol. 8, 5257–5267 (1988).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Noakes, P. G., Gautam, M., Mudd, J., Sanes, J. R. & Merlie, J. P. Nature 374, 258–262 (1995).

    ADS  CAS  Article  PubMed  Google Scholar 

  30. Ohlendieck, K. et al. Neuron 7, 499–508 (1991).

    CAS  Article  PubMed  Google Scholar 

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Gautam, M., Noakes, P., Mudd, J. et al. Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice. Nature 377, 232–236 (1995). https://doi.org/10.1038/377232a0

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