Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1994 Feb 1;124(3):381–394. doi: 10.1083/jcb.124.3.381

Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues

Reetta Vuolteenaho 1, Maria Nissinen, Kirsi Sairdo, Mary Byers, Roger Eddy, Harri Hirvonen, Thomas B Shows, Hannu Sariola, Eva Engvall, Karl Tryggvason
PMCID: PMC2119934  PMID: 8294519

Abstract

The primary structure of the human laminin M chain was determined from cDNA clones isolated from human placental libraries. The clones covered a total of 6,942 bp, with 49-bp encoding a 5' end untranslated region and 6,893-bp coding for a translated sequence. The complete human laminin M chain contains a 22-residue signal peptide and 3,088 residues of the mature M chain. The M chain has a domain structure similar to that of the human and mouse A chains. The homology between the two human laminin heavy chains is highest in the short arm region and lowest in the long arm helical domain I + II. Northern blot analysis of human fetal tissues showed that the M chain was expressed in most tissues such as cardiac muscle, pancreas, lung, spleen, kidney, adrenal gland, skin, testis, meninges, choroid plexus, and some other regions of the brain, but not in liver, thymus, and bone. In situ hybridization localized the expression of the M chain gene to cells of mesenchymal origin. In contrast, expression of the A chain was observed only in kidney, testis, neuroretina and some region of brain as determined by Northern analyses. Epithelial and endothelial cells were negative for both M and A chain gene transcripts. The gene for the human M chain (LAMM) was localized to chromosome 6q22-->23.

Full Text

The Full Text of this article is available as a PDF (2.7 MB).

Selected References

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

  1. Beck K., Hunter I., Engel J. Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J. 1990 Feb 1;4(2):148–160. doi: 10.1096/fasebj.4.2.2404817. [DOI] [PubMed] [Google Scholar]
  2. Boot-Handford R. P., Kurkinen M., Prockop D. J. Steady-state levels of mRNAs coding for the type IV collagen and laminin polypeptide chains of basement membranes exhibit marked tissue-specific stoichiometric variations in the rat. J Biol Chem. 1987 Sep 15;262(26):12475–12478. [PubMed] [Google Scholar]
  3. Cherif D., Bernard O., Berger R. Detection of single-copy genes by nonisotopic in situ hybridization on human chromosomes. Hum Genet. 1989 Mar;81(4):358–362. doi: 10.1007/BF00283691. [DOI] [PubMed] [Google Scholar]
  4. Chi H. C., Hui C. F. Primary structure of the Drosophila laminin B2 chain and comparison with human, mouse, and Drosophila laminin B1 and B2 chains. J Biol Chem. 1989 Jan 25;264(3):1543–1550. [PubMed] [Google Scholar]
  5. Cooper A. R., Kurkinen M., Taylor A., Hogan B. L. Studies on the biosynthesis of laminin by murine parietal endoderm cells. Eur J Biochem. 1981 Sep;119(1):189–197. doi: 10.1111/j.1432-1033.1981.tb05593.x. [DOI] [PubMed] [Google Scholar]
  6. Cooper A. R., MacQueen H. A. Subunits of laminin are differentially synthesized in mouse eggs and early embryos. Dev Biol. 1983 Apr;96(2):467–471. doi: 10.1016/0012-1606(83)90183-5. [DOI] [PubMed] [Google Scholar]
  7. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  8. Edgar D., Timpl R., Thoenen H. Structural requirements for the stimulation of neurite outgrowth by two variants of laminin and their inhibition by antibodies. J Cell Biol. 1988 Apr;106(4):1299–1306. doi: 10.1083/jcb.106.4.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Edgar D., Timpl R., Thoenen H. The heparin-binding domain of laminin is responsible for its effects on neurite outgrowth and neuronal survival. EMBO J. 1984 Jul;3(7):1463–1468. doi: 10.1002/j.1460-2075.1984.tb01997.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ehrig K., Leivo I., Argraves W. S., Ruoslahti E., Engvall E. Merosin, a tissue-specific basement membrane protein, is a laminin-like protein. Proc Natl Acad Sci U S A. 1990 May;87(9):3264–3268. doi: 10.1073/pnas.87.9.3264. [DOI] [PMC free article] [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. Engel J., Hunter I., Schulthess T., Beck K., Dixon T. W., Parry D. A. Assembly of laminin isoforms by triple- and double-stranded coiled-coil structures. Biochem Soc Trans. 1991 Nov;19(4):839–843. doi: 10.1042/bst0190839. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Fan Y. S., Davis L. M., Shows T. B. Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6223–6227. doi: 10.1073/pnas.87.16.6223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fukushima Y., Pikkarainen T., Kallunki T., Eddy R. L., Byers M. G., Haley L. L., Henry W. M., Tryggvason K., Shows T. B. Isolation of a human laminin B2 (LAMB2) cDNA clone and assignment of the gene to chromosome region 1q25----q31. Cytogenet Cell Genet. 1988;48(3):137–141. doi: 10.1159/000132610. [DOI] [PubMed] [Google Scholar]
  16. Haaparanta T., Uitto J., Ruoslahti E., Engvall E. Molecular cloning of the cDNA encoding human laminin A chain. Matrix. 1991 Jun;11(3):151–160. doi: 10.1016/s0934-8832(11)80153-8. [DOI] [PubMed] [Google Scholar]
  17. Holm K., Risteli L., Sariola H. Differential expression of the laminin A and B chains in chimeric kidneys. Cell Differ. 1988 Aug;24(3):223–227. doi: 10.1016/0045-6039(88)90054-1. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  20. Joseph D. R., Baker M. E. Sex hormone-binding globulin, androgen-binding protein, and vitamin K-dependent protein S are homologous to laminin A, merosin, and Drosophila crumbs protein. FASEB J. 1992 Apr;6(7):2477–2481. doi: 10.1096/fasebj.6.7.1532944. [DOI] [PubMed] [Google Scholar]
  21. Kallunki P., Sainio K., Eddy R., Byers M., Kallunki T., Sariola H., Beck K., Hirvonen H., Shows T. B., Tryggvason K. A truncated laminin chain homologous to the B2 chain: structure, spatial expression, and chromosomal assignment. J Cell Biol. 1992 Nov;119(3):679–693. doi: 10.1083/jcb.119.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kallunki P., Tryggvason K. Human basement membrane heparan sulfate proteoglycan core protein: a 467-kD protein containing multiple domains resembling elements of the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. J Cell Biol. 1992 Jan;116(2):559–571. doi: 10.1083/jcb.116.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Klein G., Ekblom M., Fecker L., Timpl R., Ekblom P. Differential expression of laminin A and B chains during development of embryonic mouse organs. Development. 1990 Nov;110(3):823–837. doi: 10.1242/dev.110.3.823. [DOI] [PubMed] [Google Scholar]
  24. Klein G., Langegger M., Timpl R., Ekblom P. Role of laminin A chain in the development of epithelial cell polarity. Cell. 1988 Oct 21;55(2):331–341. doi: 10.1016/0092-8674(88)90056-6. [DOI] [PubMed] [Google Scholar]
  25. Kleinman H. K., Ebihara I., Killen P. D., Sasaki M., Cannon F. B., Yamada Y., Martin G. R. Genes for basement membrane proteins are coordinately expressed in differentiating F9 cells but not in normal adult murine tissues. Dev Biol. 1987 Aug;122(2):373–378. doi: 10.1016/0012-1606(87)90302-2. [DOI] [PubMed] [Google Scholar]
  26. Kleinman H. K., Sephel G. C., Tashiro K., Weeks B. S., Burrous B. A., Adler S. H., Yamada Y., Martin G. R. Laminin in neuronal development. Ann N Y Acad Sci. 1990;580:302–310. doi: 10.1111/j.1749-6632.1990.tb17939.x. [DOI] [PubMed] [Google Scholar]
  27. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kusche-Gullberg M., Garrison K., MacKrell A. J., Fessler L. I., Fessler J. H. Laminin A chain: expression during Drosophila development and genomic sequence. EMBO J. 1992 Dec;11(12):4519–4527. doi: 10.1002/j.1460-2075.1992.tb05553.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kücherer-Ehret A., Pottgiesser J., Kreutzberg G. W., Thoenen H., Edgar D. Developmental loss of laminin from the interstitial extracellular matrix correlates with decreased laminin gene expression. Development. 1990 Dec;110(4):1285–1293. doi: 10.1242/dev.110.4.1285. [DOI] [PubMed] [Google Scholar]
  30. Leivo I., Engvall E. Merosin, a protein specific for basement membranes of Schwann cells, striated muscle, and trophoblast, is expressed late in nerve and muscle development. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1544–1548. doi: 10.1073/pnas.85.5.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. MacKrell A. J., Kusche-Gullberg M., Garrison K., Fessler J. H. Novel Drosophila laminin A chain reveals structural relationships between laminin subunits. FASEB J. 1993 Feb 1;7(2):375–381. doi: 10.1096/fasebj.7.2.8440414. [DOI] [PubMed] [Google Scholar]
  32. Marinkovich M. P., Lunstrum G. P., Burgeson R. E. The anchoring filament protein kalinin is synthesized and secreted as a high molecular weight precursor. J Biol Chem. 1992 Sep 5;267(25):17900–17906. [PubMed] [Google Scholar]
  33. Marinkovich M. P., Lunstrum G. P., Keene D. R., Burgeson R. E. The dermal-epidermal junction of human skin contains a novel laminin variant. J Cell Biol. 1992 Nov;119(3):695–703. doi: 10.1083/jcb.119.3.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mattei M. G., Weil D., Pribula-Conway D., Bernard M. P., Passage E., Van Cong N., Timpl R., Chu M. L. cDNA cloning, expression and mapping of human laminin B2 gene to chromosome 1q31. Hum Genet. 1988 Jul;79(3):235–241. doi: 10.1007/BF00366243. [DOI] [PubMed] [Google Scholar]
  35. Mecham R. P. Receptors for laminin on mammalian cells. FASEB J. 1991 Aug;5(11):2538–2546. doi: 10.1096/fasebj.5.11.1651264. [DOI] [PubMed] [Google Scholar]
  36. Montell D. J., Goodman C. S. Drosophila laminin: sequence of B2 subunit and expression of all three subunits during embryogenesis. J Cell Biol. 1989 Nov;109(5):2441–2453. doi: 10.1083/jcb.109.5.2441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Montell D. J., Goodman C. S. Drosophila substrate adhesion molecule: sequence of laminin B1 chain reveals domains of homology with mouse. Cell. 1988 May 6;53(3):463–473. doi: 10.1016/0092-8674(88)90166-3. [DOI] [PubMed] [Google Scholar]
  38. Nagayoshi T., Mattei M. G., Passage E., Knowlton R., Chu M. L., Uitto J. Human laminin A chain (LAMA) gene: chromosomal mapping to locus 18p11.3. Genomics. 1989 Nov;5(4):932–935. doi: 10.1016/0888-7543(89)90136-5. [DOI] [PubMed] [Google Scholar]
  39. Nissinen M., Vuolteenaho R., Boot-Handford R., Kallunki P., Tryggvason K. Primary structure of the human laminin A chain. Limited expression in human tissues. Biochem J. 1991 Jun 1;276(Pt 2):369–379. doi: 10.1042/bj2760369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. O'Rear J. J. A novel laminin B1 chain variant in avian eye. J Biol Chem. 1992 Oct 15;267(29):20555–20557. [PubMed] [Google Scholar]
  41. Patthy L. A family of laminin-related proteins controlling ectodermal differentiation in Drosophila. FEBS Lett. 1992 Feb 24;298(2-3):182–184. doi: 10.1016/0014-5793(92)80051-h. [DOI] [PubMed] [Google Scholar]
  42. Paulsson M., Saladin K., Engvall E. Structure of laminin variants. The 300-kDa chains of murine and bovine heart laminin are related to the human placenta merosin heavy chain and replace the a chain in some laminin variants. J Biol Chem. 1991 Sep 15;266(26):17545–17551. [PubMed] [Google Scholar]
  43. Paulsson M., Saladin K. Mouse heart laminin. Purification of the native protein and structural comparison with Engelbreth-Holm-Swarm tumor laminin. J Biol Chem. 1989 Nov 5;264(31):18726–18732. [PubMed] [Google Scholar]
  44. Pikkarainen T., Eddy R., Fukushima Y., Byers M., Shows T., Pihlajaniemi T., Saraste M., Tryggvason K. Human laminin B1 chain. A multidomain protein with gene (LAMB1) locus in the q22 region of chromosome 7. J Biol Chem. 1987 Aug 5;262(22):10454–10462. [PubMed] [Google Scholar]
  45. Pikkarainen T., Kallunki T., Tryggvason K. Human laminin B2 chain. Comparison of the complete amino acid sequence with the B1 chain reveals variability in sequence homology between different structural domains. J Biol Chem. 1988 May 15;263(14):6751–6758. [PubMed] [Google Scholar]
  46. Rousselle P., Lunstrum G. P., Keene D. R., Burgeson R. E. Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol. 1991 Aug;114(3):567–576. doi: 10.1083/jcb.114.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. Sasaki M., Kato S., Kohno K., Martin G. R., Yamada Y. Sequence of the cDNA encoding the laminin B1 chain reveals a multidomain protein containing cysteine-rich repeats. Proc Natl Acad Sci U S A. 1987 Feb;84(4):935–939. doi: 10.1073/pnas.84.4.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Sasaki M., Kleinman H. K., Huber H., Deutzmann R., Yamada Y. Laminin, a multidomain protein. The A chain has a unique globular domain and homology with the basement membrane proteoglycan and the laminin B chains. J Biol Chem. 1988 Nov 15;263(32):16536–16544. [PubMed] [Google Scholar]
  51. Sasaki M., Yamada Y. The laminin B2 chain has a multidomain structure homologous to the B1 chain. J Biol Chem. 1987 Dec 15;262(35):17111–17117. [PubMed] [Google Scholar]
  52. Shows T. B., Sakaguchi A. Y., Naylor S. L. Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease. Adv Hum Genet. 1982;12:341–452. doi: 10.1007/978-1-4615-8315-8_5. [DOI] [PubMed] [Google Scholar]
  53. Shows T., Eddy R., Haley L., Byers M., Henry M., Fujita T., Matsui H., Taniguchi T. Interleukin 2 (IL2) is assigned to human chromosome 4. Somat Cell Mol Genet. 1984 May;10(3):315–318. doi: 10.1007/BF01535253. [DOI] [PubMed] [Google Scholar]
  54. 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]
  55. Ushkaryov Y. A., Petrenko A. G., Geppert M., Südhof T. C. Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. Science. 1992 Jul 3;257(5066):50–56. doi: 10.1126/science.1621094. [DOI] [PubMed] [Google Scholar]
  56. Yurchenco P. D., Cheng Y. S., Colognato H. Laminin forms an independent network in basement membranes. J Cell Biol. 1992 Jun;117(5):1119–1133. doi: 10.1083/jcb.117.5.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Yurchenco P. D., Schittny J. C. Molecular architecture of basement membranes. FASEB J. 1990 Apr 1;4(6):1577–1590. doi: 10.1096/fasebj.4.6.2180767. [DOI] [PubMed] [Google Scholar]
  58. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES