Structures and interactions of syndecans

Gondelaud, Frank; Ricard‐Blum, Sylvie

doi:10.1111/febs.14828

Cited by 101 publications

(69 citation statements)

References 107 publications

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“…This observation implies that the ectodomain is dispensable for the cell surface localization of truncated syndecan-1. However, it is to be noted that our truncated syndecan-1 construct still contained the transmembrane domain and membrane-proximal four amino acids of the ectodomain that were found important for the dimerization [ 20 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

et al. 2020

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Syndecan-1 is a transmembrane heparan sulfate proteoglycan which is indispensable in the structural and functional integrity of epithelia. Normal hepatocytes display strong cell surface expression of syndecan-1; however, upon malignant transformation, they may lose it from their cell surfaces. In this study, we demonstrate that re-expression of full-length or ectodomain-deleted syndecan-1 in hepatocellular carcinoma cells downregulates phosphorylation of ERK1/2 and p38, with the truncated form exerting an even stronger effect than the full-length protein. Furthermore, overexpression of syndecan-1 in hepatoma cells is associated with a shift of heparan sulfate structure toward a highly sulfated type specific for normal liver. As a result, cell proliferation and proteolytic shedding of syndecan-1 from the cell surface are restrained, which facilitates redifferentiation of hepatoma cells to a more hepatocyte-like phenotype. Our results highlight the importance of syndecan-1 in the formation and maintenance of differentiated epithelial characteristics in hepatocytes partly via the HGF/ERK/Ets-1 signal transduction pathway. Downregulation of Ets-1 expression alone, however, was not sufficient to replicate the phenotype of syndecan-1 overexpressing cells, indicating the need for additional molecular mechanisms. Accordingly, a reporter gene assay revealed the inhibition of Ets-1 as well as AP-1 transcription factor-induced promoter activation, presumably an effect of the heparan sulfate switch.

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Section: Discussionmentioning

confidence: 99%

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

et al. 2020

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“…SDC2 is mainly expressed in endothelial cells and fibroblasts. SDC3 is expressed in neural tissues (117). SDC4 is abundant in many cell types and a soluble protein isoform lacking the transmembrane and cytoplasmic domains (118).…”

Section: Syndecanmentioning

confidence: 99%

Regulation of Macrophage and Dendritic Cell Function by Chondroitin Sulfate in Innate to Antigen-Specific Adaptive Immunity

Hatano

Watanabe

2020

Front. Immunol.

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Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a linear acidic polysaccharide comprised of repeating disaccharides, modified with sulfate groups at various positions. Except for hyaluronan (HA), GAGs are covalently bound to core proteins, forming proteoglycans (PGs). With highly negative charges, GAGs interact with a variety of physiologically active molecules, including cytokines, chemokines, and growth factors, and control cell behavior during development and in the progression of diseases, including cancer, infections, and inflammation. Heparan sulfate (HS), another type of GAG, and HA are well reported as regulators for leukocyte migration at sites of inflammation. There have been many reports on the regulation of immune cell function by HS and HA; however, regulation of immune cells by CS has not yet been fully understood. This article focuses on the regulatory function of CS in antigen-presenting cells, including macrophages and dendritic cells, and refers to CSPGs, such as versican and biglycan, and the cell surface proteoglycan, syndecan.

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“…The core protein of Sdc-1 consists of an extracellular, a transmembrane, and a cytoplasmatic domain. The extracellular part-or ectodomain-is decorated by chondroitin sulfate and at least one heparan sulfate chain (reviewed in [5,6]. Heparan sulfate (HS) consists of repeating disaccharide units of an N-acetylglucosamine and glucuronic acid.…”

Section: Introductionmentioning

confidence: 99%

Role of syndecan-1 in the interaction between dendritic cells and T cells

et al. 2020

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Syndecan-1 (Sdc-1) is a heparan sulfate proteoglycan that can bind cytokines and chemokines via its heparan sulfate side chains, and has immunomodulatory properties in experimental models. Sdc-1 expression has been reported on dendritic cells (DC) and T cells. The potential role of Sdc-1 in DC-T cell interaction has not been investigated yet. We postulate that Sdc-1 is involved in DC-T cell interaction and may influence graft survival in an allogeneic transplant model. Sdc-1 expression on bone marrow-derived DC and T cells was analyzed by flow cytometry. Unstimulated and LPS stimulated Sdc-1 deficient DC were evaluated in vitro for phenotype and stimulatory capacity in mixed lymphocyte reaction. Sdc-1 deficient T cells were evaluated for proliferative capacity and differentiation in a mixed lymphocyte reaction and a proliferation assay. Allograft survival was evaluated in a fully MHC mismatched heterotopic heart transplant model, with either Sdc-1 deficient donors or recipients. Sdc-1 was expressed on the cell surface of unstimulated and LPS matured DC. Sdc-1 deficiency had no effect on expression of co-stimulatory molecules, cytokine production or T cell stimulatory capacity as compared to WT DC. Sdc-1 expression was not detectable on WT T cells, although intracellular Sdc-1 expression could be demonstrated after ConA activation. Sdc-1 deficient T cells showed reduced proliferation upon DC or ConA stimulation and reduced IL-17 production upon ConA stimulation, compared to WT T cells. Sdc-1 deficiency of either allograft or recipient did not prolong allograft survival. In conclusion, Sdc-1 is expressed on the cell surface of DC, where its absence does not affect DC phenotype or T cell stimulatory capacity. Sdc-1 is intracellularly expressed in ConA activated T cells. Sdc-1 deficiency in T cells results in a reduced proliferative response in vitro, as induced by DC and ConA. Sdc-1 deficiency in donor or recipient does not affect allograft survival.

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Structures and interactions of syndecans

Cited by 101 publications

References 107 publications

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Regulation of Macrophage and Dendritic Cell Function by Chondroitin Sulfate in Innate to Antigen-Specific Adaptive Immunity

Role of syndecan-1 in the interaction between dendritic cells and T cells

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