Skip to main content
PMC home page
Molecular Biology of the Cell logoLink to Molecular Biology of the Cell
. 1994 Jul;5(7):797–805. doi: 10.1091/mbc.5.7.797

Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns.

C W Kim 1, O A Goldberger 1, R L Gallo 1, M Bernfield 1
PMCID: PMC301097  PMID: 7812048

Abstract

The syndecans are a gene family of four transmembrane heparan sulfate proteoglycans that bind, via their HS chains, diverse components of the cellular microenvironment. To evaluate the expression of the individual syndecans, we prepared cDNA probes to compare mRNA levels in various adult mouse tissues and cultured mouse cells representing various epithelial, fibroblastic, endothelial, and neural cell types and B cells at various stages of differentiation. We also prepared antibody probes to assess whether the extracellular domains of the individual syndecans are shed into the conditioned media of cultured cells. Our results show that all cells and tissues studied, except B-stem cells, express at least one syndecan family member; most cells and tissues express multiple syndecans. However, each syndecan family member is expressed selectively in cell-, tissue-, and development-specific patterns. The extracellular domain of all syndecan family members is shed as an intact proteoglycan. Thus, most, if not all, cells acquire a distinctive repertoire of the four syndecan family members as they differentiate, resulting in selective patterns of expression that likely reflect distinct functions.

Full text

PDF
798

Images in this article

800Image
on p.800
802Image
on p.802
803Image
on p.803
803Image
on p.803

Selected References

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

  1. Aaronson S. A., Todaro G. J. Development of 3T3-like lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40. J Cell Physiol. 1968 Oct;72(2):141–148. doi: 10.1002/jcp.1040720208. [DOI] [PubMed] [Google Scholar]
  2. Alt F., Rosenberg N., Lewis S., Thomas E., Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes. Cell. 1981 Dec;27(2 Pt 1):381–390. doi: 10.1016/0092-8674(81)90421-9. [DOI] [PubMed] [Google Scholar]
  3. Ansorge S., Schön E., Kunz D. Membrane-bound peptidases of lymphocytes: functional implications. Biomed Biochim Acta. 1991;50(4-6):799–807. [PubMed] [Google Scholar]
  4. Baciu P. C., Acaster C., Goetinck P. F. Molecular cloning and genomic organization of chicken syndecan-4. J Biol Chem. 1994 Jan 7;269(1):696–703. [PubMed] [Google Scholar]
  5. Bernfield M., Banerjee S. D. The turnover of basal lamina glycosaminoglycan correlates with epithelial morphogenesis. Dev Biol. 1982 Apr;90(2):291–305. doi: 10.1016/0012-1606(82)90378-5. [DOI] [PubMed] [Google Scholar]
  6. Bernfield M., Kokenyesi R., Kato M., Hinkes M. T., Spring J., Gallo R. L., Lose E. J. Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans. Annu Rev Cell Biol. 1992;8:365–393. doi: 10.1146/annurev.cb.08.110192.002053. [DOI] [PubMed] [Google Scholar]
  7. Burchiel S. W., Warner N. L. Cyclic AMP modulation of Fc receptor expression on a pre-B cell lymphoma. J Immunol. 1980 Mar;124(3):1016–1021. [PubMed] [Google Scholar]
  8. Carey D. J., Evans D. M., Stahl R. C., Asundi V. K., Conner K. J., Garbes P., Cizmeci-Smith G. Molecular cloning and characterization of N-syndecan, a novel transmembrane heparan sulfate proteoglycan. J Cell Biol. 1992 Apr;117(1):191–201. doi: 10.1083/jcb.117.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chernousov M. A., Carey D. J. N-syndecan (syndecan 3) from neonatal rat brain binds basic fibroblast growth factor. J Biol Chem. 1993 Aug 5;268(22):16810–16814. [PubMed] [Google Scholar]
  10. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  11. Cizmeci-Smith G., Asundi V., Stahl R. C., Teichman L. J., Chernousov M., Cowan K., Carey D. J. Regulated expression of syndecan in vascular smooth muscle cells and cloning of rat syndecan core protein cDNA. J Biol Chem. 1992 Aug 5;267(22):15729–15736. [PubMed] [Google Scholar]
  12. David G., Bai X. M., Van der Schueren B., Marynen P., Cassiman J. J., Van den Berghe H. Spatial and temporal changes in the expression of fibroglycan (syndecan-2) during mouse embryonic development. Development. 1993 Nov;119(3):841–854. doi: 10.1242/dev.119.3.841. [DOI] [PubMed] [Google Scholar]
  13. David G. Integral membrane heparan sulfate proteoglycans. FASEB J. 1993 Aug;7(11):1023–1030. doi: 10.1096/fasebj.7.11.8370471. [DOI] [PubMed] [Google Scholar]
  14. David G., Lories V., Decock B., Marynen P., Cassiman J. J., Van den Berghe H. Molecular cloning of a phosphatidylinositol-anchored membrane heparan sulfate proteoglycan from human lung fibroblasts. J Cell Biol. 1990 Dec;111(6 Pt 2):3165–3176. doi: 10.1083/jcb.111.6.3165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. David G., van der Schueren B., Marynen P., Cassiman J. J., van den Berghe H. Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells. J Cell Biol. 1992 Aug;118(4):961–969. doi: 10.1083/jcb.118.4.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Elenius K., Vainio S., Laato M., Salmivirta M., Thesleff I., Jalkanen M. Induced expression of syndecan in healing wounds. J Cell Biol. 1991 Aug;114(3):585–595. doi: 10.1083/jcb.114.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gould S. E., Upholt W. B., Kosher R. A. Syndecan 3: a member of the syndecan family of membrane-intercalated proteoglycans that is expressed in high amounts at the onset of chicken limb cartilage differentiation. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3271–3275. doi: 10.1073/pnas.89.8.3271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Greenberger J. S., Sakakeeny M. A., Humphries R. K., Eaves C. J., Eckner R. J. Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci U S A. 1983 May;80(10):2931–2935. doi: 10.1073/pnas.80.10.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hinkes M. T., Goldberger O. A., Neumann P. E., Kokenyesi R., Bernfield M. Organization and promoter activity of the mouse syndecan-1 gene. J Biol Chem. 1993 May 25;268(15):11440–11448. [PubMed] [Google Scholar]
  20. Hoak J. C., Czervionke R. L., Fry G. L., Haycraft D. L., Brotherton A. A. Role of the vascular endothelium. Philos Trans R Soc Lond B Biol Sci. 1981 Aug 18;294(1072):331–338. doi: 10.1098/rstb.1981.0109. [DOI] [PubMed] [Google Scholar]
  21. Jainchill J. L., Aaronson S. A., Todaro G. J. Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol. 1969 Nov;4(5):549–553. doi: 10.1128/jvi.4.5.549-553.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jalkanen M., Nguyen H., Rapraeger A., Kurn N., Bernfield M. Heparan sulfate proteoglycans from mouse mammary epithelial cells: localization on the cell surface with a monoclonal antibody. J Cell Biol. 1985 Sep;101(3):976–984. doi: 10.1083/jcb.101.3.976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jalkanen M., Rapraeger A., Saunders S., Bernfield M. Cell surface proteoglycan of mouse mammary epithelial cells is shed by cleavage of its matrix-binding ectodomain from its membrane-associated domain. J Cell Biol. 1987 Dec;105(6 Pt 2):3087–3096. doi: 10.1083/jcb.105.6.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Karasuyama H., Melchers F. Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur J Immunol. 1988 Jan;18(1):97–104. doi: 10.1002/eji.1830180115. [DOI] [PubMed] [Google Scholar]
  25. Khorana H. G. Rhodopsin, photoreceptor of the rod cell. An emerging pattern for structure and function. J Biol Chem. 1992 Jan 5;267(1):1–4. [PubMed] [Google Scholar]
  26. Kiefer M. C., Stephans J. C., Crawford K., Okino K., Barr P. J. Ligand-affinity cloning and structure of a cell surface heparan sulfate proteoglycan that binds basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6985–6989. doi: 10.1073/pnas.87.18.6985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kojima T., Shworak N. W., Rosenberg R. D. Molecular cloning and expression of two distinct cDNA-encoding heparan sulfate proteoglycan core proteins from a rat endothelial cell line. J Biol Chem. 1992 Mar 5;267(7):4870–4877. [PubMed] [Google Scholar]
  28. Kraemer P. M. Heparan sulfates of cultured cells. II. Acid-soluble and -precipitable species of different cell lines. Biochemistry. 1971 Apr 13;10(8):1445–1451. doi: 10.1021/bi00784a027. [DOI] [PubMed] [Google Scholar]
  29. Laskov R., Scharff M. D. Synthesis, assembly, and secretion of gamma globulin by mouse myeloma cells. I. Adaptation of the Merwin plasma cell tumor-11 to culture, cloning, and characterization of gamma globulin subunits. J Exp Med. 1970 Mar 1;131(3):515–541. doi: 10.1084/jem.131.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Leppä S., Härkönen P., Jalkanen M. Steroid-induced epithelial-fibroblastic conversion associated with syndecan suppression in S115 mouse mammary tumor cells. Cell Regul. 1991 Jan;2(1):1–11. doi: 10.1091/mbc.2.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Leppä S., Mali M., Miettinen H. M., Jalkanen M. Syndecan expression regulates cell morphology and growth of mouse mammary epithelial tumor cells. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):932–936. doi: 10.1073/pnas.89.3.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lewis S., Rosenberg N., Alt F., Baltimore D. Continuing kappa-gene rearrangement in a cell line transformed by Abelson murine leukemia virus. Cell. 1982 Oct;30(3):807–816. doi: 10.1016/0092-8674(82)90285-9. [DOI] [PubMed] [Google Scholar]
  33. Lories V., Cassiman J. J., Van den Berghe H., David G. Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts. J Biol Chem. 1992 Jan 15;267(2):1116–1122. [PubMed] [Google Scholar]
  34. López-Casillas F., Cheifetz S., Doody J., Andres J. L., Lane W. S., Massagué J. Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. Cell. 1991 Nov 15;67(4):785–795. doi: 10.1016/0092-8674(91)90073-8. [DOI] [PubMed] [Google Scholar]
  35. Makino J. K., Weissman B. E. Identification of two 36-kD phosphoproteins associated with altered differentiation in retrovirus-transformed Balb/MK-2 mouse keratinocytes. Pathobiology. 1991;59(6):384–390. doi: 10.1159/000163682. [DOI] [PubMed] [Google Scholar]
  36. Mali M., Jaakkola P., Arvilommi A. M., Jalkanen M. Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans. J Biol Chem. 1990 Apr 25;265(12):6884–6889. [PubMed] [Google Scholar]
  37. Marynen P., Zhang J., Cassiman J. J., Van den Berghe H., David G. Partial primary structure of the 48- and 90-kilodalton core proteins of cell surface-associated heparan sulfate proteoglycans of lung fibroblasts. Prediction of an integral membrane domain and evidence for multiple distinct core proteins at the cell surface of human lung fibroblasts. J Biol Chem. 1989 Apr 25;264(12):7017–7024. [PubMed] [Google Scholar]
  38. Mathey-Prevot B., Nabel G., Palacios R., Baltimore D. Abelson virus abrogation of interleukin-3 dependence in a lymphoid cell line. Mol Cell Biol. 1986 Nov;6(11):4133–4135. doi: 10.1128/mcb.6.11.4133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Novotny W. F., Palmier M., Wun T. C., Broze G. J., Jr, Miletich J. P. Purification and properties of heparin-releasable lipoprotein-associated coagulation inhibitor. Blood. 1991 Jul 15;78(2):394–400. [PubMed] [Google Scholar]
  40. Owens R. B. Glandular epithelial cells from mice: a method for selective cultivation. J Natl Cancer Inst. 1974 Apr;52(4):1375–1378. doi: 10.1093/jnci/52.4.1375. [DOI] [PubMed] [Google Scholar]
  41. Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
  42. Rapraeger A., Bernfield M. Cell surface proteoglycan of mammary epithelial cells. Protease releases a heparan sulfate-rich ectodomain from a putative membrane-anchored domain. J Biol Chem. 1985 Apr 10;260(7):4103–4109. [PubMed] [Google Scholar]
  43. Raulo E., Chernousov M. A., Carey D. J., Nolo R., Rauvala H. Isolation of a neuronal cell surface receptor of heparin binding growth-associated molecule (HB-GAM). Identification as N-syndecan (syndecan-3). J Biol Chem. 1994 Apr 29;269(17):12999–13004. [PubMed] [Google Scholar]
  44. Reznikoff C. A., Brankow D. W., Heidelberger C. Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res. 1973 Dec;33(12):3231–3238. [PubMed] [Google Scholar]
  45. Ridley R. C., Xiao H., Hata H., Woodliff J., Epstein J., Sanderson R. D. Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen. Blood. 1993 Feb 1;81(3):767–774. [PubMed] [Google Scholar]
  46. Sanderson R. D., Bernfield M. Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9562–9566. doi: 10.1073/pnas.85.24.9562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sanderson R. D., Hinkes M. T., Bernfield M. Syndecan-1, a cell-surface proteoglycan, changes in size and abundance when keratinocytes stratify. J Invest Dermatol. 1992 Oct;99(4):390–396. doi: 10.1111/1523-1747.ep12616103. [DOI] [PubMed] [Google Scholar]
  48. Sanderson R. D., Lalor P., Bernfield M. B lymphocytes express and lose syndecan at specific stages of differentiation. Cell Regul. 1989 Nov;1(1):27–35. doi: 10.1091/mbc.1.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Saunders S., Bernfield M. Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix. J Cell Biol. 1988 Feb;106(2):423–430. doi: 10.1083/jcb.106.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Saunders S., Jalkanen M., O'Farrell S., Bernfield M. Molecular cloning of syndecan, an integral membrane proteoglycan. J Cell Biol. 1989 Apr;108(4):1547–1556. doi: 10.1083/jcb.108.4.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Snyder E. Y., Deitcher D. L., Walsh C., Arnold-Aldea S., Hartwieg E. A., Cepko C. L. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell. 1992 Jan 10;68(1):33–51. doi: 10.1016/0092-8674(92)90204-p. [DOI] [PubMed] [Google Scholar]
  52. Solursh M., Reiter R. S., Jensen K. L., Kato M., Bernfield M. Transient expression of a cell surface heparan sulfate proteoglycan (syndecan) during limb development. Dev Biol. 1990 Jul;140(1):83–92. doi: 10.1016/0012-1606(90)90055-n. [DOI] [PubMed] [Google Scholar]
  53. Spring J., Paine-Saunders S. E., Hynes R. O., Bernfield M. Drosophila syndecan: conservation of a cell-surface heparan sulfate proteoglycan. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3334–3338. doi: 10.1073/pnas.91.8.3334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Stipp C. S., Litwack E. D., Lander A. D. Cerebroglycan: an integral membrane heparan sulfate proteoglycan that is unique to the developing nervous system and expressed specifically during neuronal differentiation. J Cell Biol. 1994 Jan;124(1-2):149–160. doi: 10.1083/jcb.124.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sutherland A. E., Sanderson R. D., Mayes M., Seibert M., Calarco P. G., Bernfield M., Damsky C. H. Expression of syndecan, a putative low affinity fibroblast growth factor receptor, in the early mouse embryo. Development. 1991 Sep;113(1):339–351. doi: 10.1242/dev.113.1.339. [DOI] [PubMed] [Google Scholar]
  56. Trautman M. S., Kimelman J., Bernfield M. Developmental expression of syndecan, an integral membrane proteoglycan, correlates with cell differentiation. Development. 1991 Jan;111(1):213–220. doi: 10.1242/dev.111.1.213. [DOI] [PubMed] [Google Scholar]
  57. Vainio S., Jalkanen M., Bernfield M., Saxén L. Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney. Dev Biol. 1992 Aug;152(2):221–232. doi: 10.1016/0012-1606(92)90130-9. [DOI] [PubMed] [Google Scholar]
  58. Vihinen T., Auvinen P., Alanen-Kurki L., Jalkanen M. Structural organization and genomic sequence of mouse syndecan-1 gene. J Biol Chem. 1993 Aug 15;268(23):17261–17269. [PubMed] [Google Scholar]
  59. Warner N. L., Daley M. J., Richey J., Spellman C. Flow cytometry analysis of murine B cell lymphoma differentiation. Immunol Rev. 1979;48:197–243. doi: 10.1111/j.1600-065x.1979.tb00304.x. [DOI] [PubMed] [Google Scholar]
  60. Yeaman C., Rapraeger A. C. Post-transcriptional regulation of syndecan-1 expression by cAMP in peritoneal macrophages. J Cell Biol. 1993 Aug;122(4):941–950. doi: 10.1083/jcb.122.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yuspa S. H., Koehler B., Kulesz-Martin M., Hennings H. Clonal growth of mouse epidermal cells in medium with reduced calcium concentration. J Invest Dermatol. 1981 Feb;76(2):144–146. doi: 10.1111/1523-1747.ep12525490. [DOI] [PubMed] [Google Scholar]

Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology

RESOURCES