Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1996 Dec 2;135(6):1583–1592. doi: 10.1083/jcb.135.6.1583

Native chick laminin-4 containing the beta 2 chain (s-laminin) promotes motor axon growth

PMCID: PMC2133966  PMID: 8978824

Abstract

After denervation of muscle, motor axons reinnervate original synaptic sites. A recombinant fragment of the synapse specific laminin beta 2 chain (s-laminin) was reported to inhibit motor axon growth. Consequently, a specific sequence (leucine-arginine-glutamate, LRE) of the laminin beta 2 chain was proposed to act as a stop signal and to mediate specific reinnervation at the neuromuscular junction (Porter, B.E., J. Weis, and J.R. Sanes. 1995. Neuron. 14:549-559). We demonstrate here that native chick laminin-4, which contains the beta 2 chain and is present in the synaptic basement membrane, does not inhibit but rather promotes motor axon growth. In native heterotrimeric laminin, the LRE sequence of the beta 2 chain is found in a triple coiled-coil region that is formed by all three subunits. We show here that the effect of LRE depends on the structural context. Whereas a recombinant randomly coiled LRE peptide indeed inhibited outgrowth by chick motoneurons, a small recombinant triple coiled-coil protein containing this sequence did not.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

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

  1. Aigner L., Arber S., Kapfhammer J. P., Laux T., Schneider C., Botteri F., Brenner H. R., Caroni P. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell. 1995 Oct 20;83(2):269–278. doi: 10.1016/0092-8674(95)90168-x. [DOI] [PubMed] [Google Scholar]
  2. Beck K., Gambee J. E., Bohan C. A., Bächinger H. P. The C-terminal domain of cartilage matrix protein assembles into a triple-stranded alpha-helical coiled-coil structure. J Mol Biol. 1996 Mar 15;256(5):909–923. doi: 10.1006/jmbi.1996.0137. [DOI] [PubMed] [Google Scholar]
  3. Brandenberger R., Chiquet M. Distinct heparin-binding and neurite-promoting properties of laminin isoforms isolated from chick heart. J Cell Sci. 1995 Sep;108(Pt 9):3099–3108. doi: 10.1242/jcs.108.9.3099. [DOI] [PubMed] [Google Scholar]
  4. Brown J. C., Wiedemann H., Timpl R. Protein binding and cell adhesion properties of two laminin isoforms (AmB1eB2e, AmB1sB2e) from human placenta. J Cell Sci. 1994 Jan;107(Pt 1):329–338. doi: 10.1242/jcs.107.1.329. [DOI] [PubMed] [Google Scholar]
  5. Brubacher D., Wehrle-Haller B., Chiquet M. Chick laminin: isolation by monoclonal antibodies and differential distribution of variants in the embryo. Exp Cell Res. 1991 Dec;197(2):290–299. doi: 10.1016/0014-4827(91)90435-w. [DOI] [PubMed] [Google Scholar]
  6. Burgeson R. E., Chiquet M., Deutzmann R., Ekblom P., Engel J., Kleinman H., Martin G. R., Meneguzzi G., Paulsson M., Sanes J. A new nomenclature for the laminins. Matrix Biol. 1994 Apr;14(3):209–211. doi: 10.1016/0945-053x(94)90184-8. [DOI] [PubMed] [Google Scholar]
  7. Chang S., Rathjen F. G., Raper J. A. Extension of neurites on axons is impaired by antibodies against specific neural cell surface glycoproteins. J Cell Biol. 1987 Feb;104(2):355–362. doi: 10.1083/jcb.104.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen Y. H., Yang J. T., Chau K. H. Determination of the helix and beta form of proteins in aqueous solution by circular dichroism. Biochemistry. 1974 Jul 30;13(16):3350–3359. doi: 10.1021/bi00713a027. [DOI] [PubMed] [Google Scholar]
  9. Cohen C., Parry D. A. Alpha-helical coiled coils and bundles: how to design an alpha-helical protein. Proteins. 1990;7(1):1–15. doi: 10.1002/prot.340070102. [DOI] [PubMed] [Google Scholar]
  10. Dohrmann U., Edgar D., Sendtner M., Thoenen H. Muscle-derived factors that support survival and promote fiber outgrowth from embryonic chick spinal motor neurons in culture. Dev Biol. 1986 Nov;118(1):209–221. doi: 10.1016/0012-1606(86)90089-8. [DOI] [PubMed] [Google Scholar]
  11. Ekblom M., Klein G., Mugrauer G., Fecker L., Deutzmann R., Timpl R., Ekblom P. Transient and locally restricted expression of laminin A chain mRNA by developing epithelial cells during kidney organogenesis. Cell. 1990 Jan 26;60(2):337–346. doi: 10.1016/0092-8674(90)90748-4. [DOI] [PubMed] [Google Scholar]
  12. Engvall E., Earwicker D., Haaparanta T., Ruoslahti E., Sanes J. R. Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regul. 1990 Sep;1(10):731–740. doi: 10.1091/mbc.1.10.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goodman S. L., Newgreen D. Do cells show an inverse locomotory response to fibronectin and laminin substrates? EMBO J. 1985 Nov;4(11):2769–2771. doi: 10.1002/j.1460-2075.1985.tb04002.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Greve J. M., Gottlieb D. I. Monoclonal antibodies which alter the morphology of cultured chick myogenic cells. J Cell Biochem. 1982;18(2):221–229. doi: 10.1002/jcb.1982.240180209. [DOI] [PubMed] [Google Scholar]
  15. Gribskov M., Devereux J., Burgess R. R. The codon preference plot: graphic analysis of protein coding sequences and prediction of gene expression. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):539–549. doi: 10.1093/nar/12.1part2.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Haudenschild D. R., Tondravi M. M., Hofer U., Chen Q., Goetinck P. F. The role of coiled-coil alpha-helices and disulfide bonds in the assembly and stabilization of cartilage matrix protein subunits. A mutational analysis. J Biol Chem. 1995 Sep 29;270(39):23150–23154. doi: 10.1074/jbc.270.39.23150. [DOI] [PubMed] [Google Scholar]
  17. Hauser N., Paulsson M. Native cartilage matrix protein (CMP). A compact trimer of subunits assembled via a coiled-coil alpha-helix. J Biol Chem. 1994 Oct 14;269(41):25747–25753. [PubMed] [Google Scholar]
  18. Henderson C. E., Camu W., Mettling C., Gouin A., Poulsen K., Karihaloo M., Rullamas J., Evans T., McMahon S. B., Armanini M. P. Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature. 1993 May 20;363(6426):266–270. doi: 10.1038/363266a0. [DOI] [PubMed] [Google Scholar]
  19. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. doi: 10.1016/0378-1119(89)90358-2. [DOI] [PubMed] [Google Scholar]
  20. Hoffmann A., Roeder R. G. Purification of his-tagged proteins in non-denaturing conditions suggests a convenient method for protein interaction studies. Nucleic Acids Res. 1991 Nov 25;19(22):6337–6338. doi: 10.1093/nar/19.22.6337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hunter D. D., Cashman N., Morris-Valero R., Bulock J. W., Adams S. P., Sanes J. R. An LRE (leucine-arginine-glutamate)-dependent mechanism for adhesion of neurons to S-laminin. J Neurosci. 1991 Dec;11(12):3960–3971. doi: 10.1523/JNEUROSCI.11-12-03960.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hunter D. D., Porter B. E., Bulock J. W., Adams S. P., Merlie J. P., Sanes J. R. Primary sequence of a motor neuron-selective adhesive site in the synaptic basal lamina protein S-laminin. Cell. 1989 Dec 1;59(5):905–913. doi: 10.1016/0092-8674(89)90613-2. [DOI] [PubMed] [Google Scholar]
  23. Hunter D. D., Shah V., Merlie J. P., Sanes J. R. A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. Nature. 1989 Mar 16;338(6212):229–234. doi: 10.1038/338229a0. [DOI] [PubMed] [Google Scholar]
  24. Iivanainen A., Sainio K., Sariola H., Tryggvason K. Primary structure and expression of a novel human laminin alpha 4 chain. FEBS Lett. 1995 May 29;365(2-3):183–188. doi: 10.1016/0014-5793(95)00462-i. [DOI] [PubMed] [Google Scholar]
  25. Kammerer R. A., Antonsson P., Schulthess T., Fauser C., Engel J. Selective chain recognition in the C-terminal alpha-helical coiled-coil region of laminin. J Mol Biol. 1995 Jun 30;250(1):64–73. doi: 10.1006/jmbi.1995.0358. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Lagenaur C., Lemmon V. An L1-like molecule, the 8D9 antigen, is a potent substrate for neurite extension. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7753–7757. doi: 10.1073/pnas.84.21.7753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Letinsky M. S., Fischbeck K. H., McMahan U. J. Precision of reinnervation of original postsynaptic sites in frog muscle after a nerve crush. J Neurocytol. 1976 Dec;5(6):691–718. doi: 10.1007/BF01181582. [DOI] [PubMed] [Google Scholar]
  29. Lupas A., Van Dyke M., Stock J. Predicting coiled coils from protein sequences. Science. 1991 May 24;252(5009):1162–1164. doi: 10.1126/science.252.5009.1162. [DOI] [PubMed] [Google Scholar]
  30. Miner J. H., Lewis R. M., Sanes J. R. Molecular cloning of a novel laminin chain, alpha 5, and widespread expression in adult mouse tissues. J Biol Chem. 1995 Dec 1;270(48):28523–28526. doi: 10.1074/jbc.270.48.28523. [DOI] [PubMed] [Google Scholar]
  31. Müller U., Bossy B., Venstrom K., Reichardt L. F. Integrin alpha 8 beta 1 promotes attachment, cell spreading, and neurite outgrowth on fibronectin. Mol Biol Cell. 1995 Apr;6(4):433–448. doi: 10.1091/mbc.6.4.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Noakes P. G., Miner J. H., Gautam M., Cunningham J. M., Sanes J. R., Merlie J. P. The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet. 1995 Aug;10(4):400–406. doi: 10.1038/ng0895-400. [DOI] [PubMed] [Google Scholar]
  34. Paulsson M. The role of Ca2+ binding in the self-aggregation of laminin-nidogen complexes. J Biol Chem. 1988 Apr 15;263(11):5425–5430. [PubMed] [Google Scholar]
  35. Pikkarainen T., Schulthess T., Engel J., Tryggvason K. Recombinant laminin B1 chains exhibit intact short-arm domains but do not form oligomeric molecules. Eur J Biochem. 1992 Oct 15;209(2):571–582. doi: 10.1111/j.1432-1033.1992.tb17322.x. [DOI] [PubMed] [Google Scholar]
  36. Pilar G., Landmesser L., Burstein L. Competition for survival among developing ciliary ganglion cells. J Neurophysiol. 1980 Jan;43(1):233–254. doi: 10.1152/jn.1980.43.1.233. [DOI] [PubMed] [Google Scholar]
  37. Porter B. E., Weis J., Sanes J. R. A motoneuron-selective stop signal in the synaptic protein S-laminin. Neuron. 1995 Mar;14(3):549–559. doi: 10.1016/0896-6273(95)90311-9. [DOI] [PubMed] [Google Scholar]
  38. Ryan M. C., Tizard R., VanDevanter D. R., Carter W. G. Cloning of the LamA3 gene encoding the alpha 3 chain of the adhesive ligand epiligrin. Expression in wound repair. J Biol Chem. 1994 Sep 9;269(36):22779–22787. [PubMed] [Google Scholar]
  39. Sanes J. R., Engvall E., Butkowski R., Hunter D. D. Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere. J Cell Biol. 1990 Oct;111(4):1685–1699. doi: 10.1083/jcb.111.4.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sanes J. R., Marshall L. M., McMahan U. J. Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. J Cell Biol. 1978 Jul;78(1):176–198. doi: 10.1083/jcb.78.1.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  42. Spring J., Beck K., Chiquet-Ehrismann R. Two contrary functions of tenascin: dissection of the active sites by recombinant tenascin fragments. Cell. 1989 Oct 20;59(2):325–334. doi: 10.1016/0092-8674(89)90294-8. [DOI] [PubMed] [Google Scholar]
  43. Syfrig J., Mann K., Paulsson M. An abundant chick gizzard integrin is the avian alpha 1 beta 1 integrin heterodimer and functions as a divalent cation-dependent collagen IV receptor. Exp Cell Res. 1991 Jun;194(2):165–173. doi: 10.1016/0014-4827(91)90349-y. [DOI] [PubMed] [Google Scholar]
  44. Timpl R., Brown J. C. The laminins. Matrix Biol. 1994 Aug;14(4):275–281. doi: 10.1016/0945-053x(94)90192-9. [DOI] [PubMed] [Google Scholar]
  45. Timpl R., Rohde H., Robey P. G., Rennard S. I., Foidart J. M., Martin G. R. Laminin--a glycoprotein from basement membranes. J Biol Chem. 1979 Oct 10;254(19):9933–9937. [PubMed] [Google Scholar]
  46. Varnum-Finney B., Venstrom K., Muller U., Kypta R., Backus C., Chiquet M., Reichardt L. F. The integrin receptor alpha 8 beta 1 mediates interactions of embryonic chick motor and sensory neurons with tenascin-C. Neuron. 1995 Jun;14(6):1213–1222. doi: 10.1016/0896-6273(95)90268-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Weaver C. D., Yoshida C. K., de Curtis I., Reichardt L. F. Expression and in vitro function of beta 1-integrin laminin receptors in the developing avian ciliary ganglion. J Neurosci. 1995 Jul;15(7 Pt 2):5275–5285. doi: 10.1523/JNEUROSCI.15-07-05275.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wehrle-Haller B., Chiquet M. Dual function of tenascin: simultaneous promotion of neurite growth and inhibition of glial migration. J Cell Sci. 1993 Oct;106(Pt 2):597–610. doi: 10.1242/jcs.106.2.597. [DOI] [PubMed] [Google Scholar]
  49. Wewer U. M., Gerecke D. R., Durkin M. E., Kurtz K. S., Mattei M. G., Champliaud M. F., Burgeson R. E., Albrechtsen R. Human beta 2 chain of laminin (formerly S chain): cDNA cloning, chromosomal localization, and expression in carcinomas. Genomics. 1994 Nov 15;24(2):243–252. doi: 10.1006/geno.1994.1612. [DOI] [PubMed] [Google Scholar]
  50. Woolfson D. N., Alber T. Predicting oligomerization states of coiled coils. Protein Sci. 1995 Aug;4(8):1596–1607. doi: 10.1002/pro.5560040818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. de Curtis I., Reichardt L. F. Function and spatial distribution in developing chick retina of the laminin receptor alpha 6 beta 1 and its isoforms. Development. 1993 Jun;118(2):377–388. doi: 10.1242/dev.118.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES