Alternative titles; symbols
HGNC Approved Gene Symbol: SDC4
Cytogenetic location: 20q13.12 Genomic coordinates (GRCh38): 20:45,325,288-45,348,424 (from NCBI)
The syndecans are transmembrane heparan sulfate proteoglycans that appear to act as receptors or coreceptors involved in intracellular communication. Syndecan-4 was isolated from rat endothelial cells, as ryudocan, by Kojima et al. (1992) and from human epithelial and fibroblastic cells, under the designation amphiglycan, by David et al. (1992).
Using yeast 2-hybrid, immunoprecipitation, and in vitro binding assays, Baciu et al. (2000) showed that chicken syndesmos (NUDT16L1; 617338) interacted with the cytoplasmic domain of Sdc4. Syndesmos and Sdc4 colocalized in ventral plasma membrane adhesion plaques in transfected xylotransferase-deficient CHO cells.
Bobardt et al. (2003) demonstrated that syndecans, including SDC4, can function as in trans HIV receptors via binding of HIV-1 gp120 to the syndecan heparan sulfate chains. Flow cytometric analysis demonstrated SDC expression on endothelial cells. HIV bound to SDC on endothelial cell lines maintained its infectivity for at least 1 week, compared with less than 1 day for unbound virus. Bobardt et al. (2003) suggested that SDC-rich endothelial cells lining the vasculature can provide a microenvironment that boosts HIV replication in T cells.
Echtermeyer et al. (2009) found that SDC4 expression was upregulated in human osteoarthritis, and that its expression correlated with severity of disease. Sdc4 was also upregulated in rat and mouse models of osteoarthritis. Deletion of the Sdc4 gene or treatment with Sdc4-blocking antibodies protected mice from proteoglycan loss and reduced cartilage destruction in a surgically-induced model of osteoarthritis. Echtermeyer et al. (2009) found that Sdc4 controls a pathway that involves Erk1 (MAPK3; 601795)/Erk2 (MAPK1; 176948)-induced activation and release of Mmp3 (185250), followed by activation of the aggrecanase Adamts5 (605007) at the chondrocyte cell surface.
Yu et al. (1995) cloned the human ryudocan promoter. Analysis of the sequence revealed the presence of several potential sites for nuclear transcription factor binding.
By analysis of interspecific backcrosses, Spring et al. (1994) mapped the Synd4 gene to distal mouse chromosome 2, very close to the Ada gene. Kojima et al. (1993) mapped the human SYND4 gene to chromosome 20q12-q13, as would be predicted from the mouse location within no more than 2.2 cM of Ada. The BMYC gene is probably located on human chromosome 20 and has been shown to be located on mouse chromosome 2 (Ingvarsson et al., 1988; Asker et al., 1989). Although BMYC is a nonfunctional MYC-related gene, its location on chromosome 2 and chromosome 20 in the mouse and the human, respectively, extends the observation of Spring et al. (1994) that 4 members of the MYC gene family and 4 members of the syndecan gene family are closely situated on 4 different chromosomes.
Syndecan-4 is upregulated in skin dermis after wounding. Echtermeyer et al. (2001) generated mice in which the Sdc4 gene was disrupted by homologous recombination in embryonic stem cells to test the hypothesis that syndecan-4 contributes to wound repair. Mice heterozygous or homozygous for the disrupted Sdc4 gene were viable, fertile, and microscopically indistinguishable from wildtype littermates. Compared with wildtype littermates, mice heterozygous or homozygous for the disrupted gene had statistically significantly delayed healing of skin wounds and impaired angiogenesis in the granulation tissue.
Cornelison et al. (2004) found that, while there were fewer apparent defects in Sdc4 -/- mouse muscle than in Sdc3 (186357) -/- muscle, Sdc4 -/- explanted satellite cells were deficient in activation, proliferation, Myod (159970) expression, myotube fusion, and differentiation. Sdc4 -/- satellite cells failed to reconstitute damaged muscle, suggesting a unique requirement for SDC4 in satellite cell function.
Asker, C., Steinitz, M., Andersson, K., Sumegi, J., Klein, G., Ingvarsson, S. Nucleotide sequence of the rat Bmyc gene.. Oncogene 4: 1523-1527, 1989. [PubMed: 2687773]
Baciu, P. C., Saoncella, S., Lee, S. H., Denhez, F., Leuthardt, D., Goetinck, P. F. Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization. J. Cell Sci. 113: 315-324, 2000. [PubMed: 10633082] [Full Text: https://doi.org/10.1242/jcs.113.2.315]
Bobardt, M. D., Saphire, A. C. S., Hung, H.-C., Yu, X., Van der Schueren, B., Zhang, Z., David, G., Gallay, P. A. Syndecan captures, protects, and transmits HIV to T lymphocytes. Immunity 18: 27-39, 2003. [PubMed: 12530973] [Full Text: https://doi.org/10.1016/s1074-7613(02)00504-6]
Cornelison, D. D. W., Wilcox-Adelman, S. A., Goetinck, P. F., Rauvala, H., Rapraeger, A. C., Olwin, B. B. Essential and separable roles for syndecan-3 and syndecan-4 in skeletal muscle development and regeneration. Genes Dev. 18: 2231-2236, 2004. [PubMed: 15371336] [Full Text: https://doi.org/10.1101/gad.1214204]
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. 118: 961-969, 1992. [PubMed: 1500433] [Full Text: https://doi.org/10.1083/jcb.118.4.961]
Echtermeyer, F., Bertrand, J., Dreier, R., Meinecke, I., Neugebauer, K., Fuerst, M., Lee, Y. J., Song, Y. W., Herzog, C., Theilmeier, G., Pap, T. Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nature Med. 15: 1072-1076, 2009. [PubMed: 19684582] [Full Text: https://doi.org/10.1038/nm.1998]
Echtermeyer, F., Streit, M., Wilcox-Adelman, S., Saoncella, S., Denhez, F., Detmar, M., Goetinck, P. F. Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4. J. Clin. Invest. 107: R9-R14, 2001. [PubMed: 11160142] [Full Text: https://doi.org/10.1172/JCI10559]
Ingvarsson, S., Sundaresan, S., Jin, P., Francke, U., Asker, C., Sumegi, J., Klein, G., Sejersen, T. Chromosome localization and expression pattern of Lmyc and Bmyc in murine embryonal carcinoma cells. Oncogene 3: 679-685, 1988. [PubMed: 2577870]
Kojima, T., Inazawa, J., Takamatsu, J., Rosenberg, R. D., Saito, H. Human ryudocan core protein: molecular cloning and characterization of the cDNA, and chromosomal localization of the gene. Biochem. Biophys. Res. Commun. 190: 814-822, 1993. [PubMed: 7916598] [Full Text: https://doi.org/10.1006/bbrc.1993.1122]
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. 267: 4870-4877, 1992. [PubMed: 1537865]
Spring, J., Goldberger, O. A., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Bernfield, M. Mapping of the syndecan genes in the mouse: linkage with members of the Myc gene family. Genomics 21: 597-601, 1994. [PubMed: 7959737] [Full Text: https://doi.org/10.1006/geno.1994.1319]
Yu, H., Humphries, D. E., Watkins, M., Karlinsky, J. B. Molecular cloning of the human ryudocan promoter. Biochem. Biophys. Res. Commun. 212: 1139-1144, 1995. [PubMed: 7626103] [Full Text: https://doi.org/10.1006/bbrc.1995.2087]