Disease relevance of Sdc4

• Cooperation of syndecan-2 and syndecan-4 among cell surface heparan sulfate proteoglycans in the actin cytoskeletal organization of Lewis lung carcinoma cells [1].
• Role of Syndecan-4 in the cellular invasion of Orientia tsutsugamushi [2].
• The provirus integration site was located 5.5 kb upstream of the first exon of the syndecan-4 gene, which encodes a heparan sulphate proteoglycan implicated in growth factor activation and protein kinase C distribution in focal adhesions [3].
• Taken together, it is suggested that syndecan-4 is induced by hypoxia stimuli in ischemic heart tissues, and may function as a tissue-repair molecule via biological mediators such as heparin-binding growth factors [4].
• In this study, we measured plasma levels of syndecan-4 in patients with acute myocardial infarction using an enzyme-immunoassay, and found that they were extremely high, with a peak of average (10.5 +/- 5.6 ng/ml, 2 weeks after onset), as compared with those in normal subjects (0.078 +/- 0.030 ng/ml) (p < 0.001) [4].

Psychiatry related information on Sdc4

• Syndecan-4 as a molecule involved in defense mechanisms [5].

High impact information on Sdc4

• This is consistent with recent in vitro data indicating a need for signaling via syndecan-4 for focal adhesion formation, and reports that overexpression of proteins that bind syndecan-4 can modify cell adhesion and migration [6].
• Syndecan-3 and syndecan-4 function as coreceptors for tyrosine kinases and in cell adhesion [7].
• While there are fewer apparent defects in syndecan-4(-/-) muscle, explanted satellite cells are deficient in activation, proliferation, MyoD expression, myotube fusion, and differentiation [7].
• Syndecan-4 is upregulated in skin dermis after wounding, and, in cultured fibroblasts adherent to the ECM protein fibronectin, this proteoglycan signals cooperatively with beta1 integrins [8].
• In this study, we generated mice in which the syndecan-4 gene was disrupted by homologous recombination in embryonic stem cells to test the hypothesis that syndecan-4 contributes to wound repair [8].

Biological context of Sdc4

• Syndecan-4 is a transmembrane heparan sulfate proteoglycan that co-operates with integrins during cell-matrix interactions for the assembly of focal adhesions and actin stress fibers and in the phosphorylation of focal adhesion kinase (FAK) on Tyr397 [9].
• Synectin, syndecan-4 cytoplasmic domain binding PDZ protein, inhibits cell migration [10].
• The syndecan-4 dependent effect of FGF-1, -2 and -7 on the transcriptional activity of IRS expressed genes and of genes involved in cell proliferation reveals a number of different response patterns [11].
• In vivo, the vibrissae of syndecan-4 null mice are shorter and have a smaller diameter than those of wild-type mice and this phenotype may result from a suboptimal response to growth factors [11].
• We have mapped the genes for syndecan-2 to chromosome 15, syndecan-3 to chromosome 4, and syndecan-4 to chromosome 2 in the mouse [12].

Anatomical context of Sdc4

• Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration [13].
• Syndecan-4 dependent FGF stimulation of mouse vibrissae growth [11].
• Syndecan-4 is expressed on keratinocytes that make up the inner root sheath of the vibrissa [11].
• Immunohistochemistry also demonstrates syndecan-4 expression in atretic follicles with apoptosis [14].
• Our results implicate syndecan-4 activation in a direct role in focal adhesion regulation [15].

Associations of Sdc4 with chemical compounds

• The cell-surface heparan sulfate proteoglycan syndecan-4 acts in conjunction with the alpha(5)beta(1) integrin to promote the formation of actin stress fibers and focal adhesions in fibronectin (FN)-adherent cells [15].
• The CS chains of the two syndecans comprised nonsulfated, 4-O-, 6-O-, and 4,6-O-disulfated N-acetylgalactosamine-containing disaccharide units and were significantly different, with a higher degree of sulfation for syndecan-4 [16].
• Activation of Rho, with lysophosphatidic acid (LPA), or protein kinase C, using the phorbol ester phorbol 12-myristate 13-acetate, or clustering of syndecan-4 with antibodies directed against its extracellular domain will stimulate formation of focal adhesions and stress fibers in CBD-adherent fibroblasts [15].
• The signal from the cell-binding domain is mediated by integrins, whereas the signal from the heparin-binding domain is recognized by heparan sulfate proteoglycans, of which syndecan-4 has been hypothesized to be involved in focal adhesion formation [17].
• Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice [18].

Physical interactions of Sdc4

• Dynamin II interacts with syndecan-4, a regulator of focal adhesion and stress-fiber formation [19].

Co-localisations of Sdc4

• In quiescent cells, dynamin II is evenly distributed in the cytoplasm and colocalizes with syndecan-4 near the nucleus [19].

Regulatory relationships of Sdc4

• Primary cardiac myocytes collected from the wild type C57/129 but not the homozygous TNF-alpha-/- knockout mice were able to induce syndecan-4 expression in ECV cells when cultured under hypoxic conditions [20].
• Ultrasound exerts an influence downstream of syndecan-4 and PKCalpha to specifically activate Rac1, itself a critical regulator of tissue repair, and to a lesser extent RhoA [21].

Other interactions of Sdc4

• Once activated, all satellite cells maintain expression of syndecan-3 and syndecan-4 for at least 96 h, also implicating these HSPGs in muscle regeneration [13].
• Screening of a yeast two-hybrid library with a cytoplasmic domain of rat syndecan-4 identified a novel binding partner, here termed synectin [10].
• Compared with syndecan-4 expression, syndecan-1 and -3 are expressed more abundantly in postovulatory follicles and the corpora lutea, but less in the type 4-5b follicles and much less in the atretic follicles [14].
• Syndecan-4 is also required for tenascin-C action [22].
• Heparan sulfate, chondroitin-6-sulfate, versican, perlecan, and syndecan-4, although exhibiting some variation in expression were detected during all phases of the migratory process [23].
• Cell-bound SD-4 ligated by DC-HIL or cross-linked by anti-SD-4 Ab attenuated anti-CD3 responses, whereas knocked-down SD-4 expression led to enhanced T cell response to APC [24].

Analytical, diagnostic and therapeutic context of Sdc4

• In the present study we examined the growth response of mouse vibrissae to HSPG-binding growth factors as a function of the presence or absence of syndecan-4 in an organ culture system [11].
• Herein, we demonstrate that syndecan-4 is expressed in the granulosa cells of type 4-5b follicles and, most intensely, in those of the atretic follicles in the mouse ovary, as revealed by in situ hybridization [14].
• Molecular cloning, genomic organization, promoter activity, and tissue-specific expression of the mouse ryudocan gene [25].
• Specific oligonucleotide probes were obtained for ryudocan and syndecan by polymerase chain reaction, and the corresponding cDNAs were isolated from a RFP-EC library [26].
• Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared with wild-type controls [18].

References