Syndecans: proteoglycan regulators of cell-surface microdomains?

Couchman, John R.

doi:10.1038/nrm1257

Cited by 382 publications

(402 citation statements)

References 110 publications

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“…It is interesting to have identified an HSPG that binds a chemokine in the setting of chronic inflammation, because emerging evidence suggests that syndecans have important functions. Their core proteins can signal, and differences between syndecans appear to exist with regard to their intracellular signaling mechanisms (6). It is also apparent that syndecan core proteins may be involved in forming membrane rafts, concentrating ligands in membrane microdomains and internalizing ligands in vesicles (6,(67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

“…The 4 syndecans, designated syndecan-1, -2, -3, and -4, have protein cores with characteristic structural domains (4). The variable ectodomain, which is exposed to the extracellular environment, contains 3-5 HS chains and is attached to the cell membrane via a hydrophobic transmembrane segment (5,6). In addition, there is an intracellular domain containing peptide sequences that serve as substrates for cellular kinases, enabling syndecans to act as signaling molecules (7,8).…”

mentioning

confidence: 99%

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Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

Patterson

Gardner

Shaw

et al. 2005

Arthritis & Rheumatism

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

Patterson

Gardner

Shaw

et al. 2005

Arthritis & Rheumatism

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“…(Filla et al 2004;Chen et al 2005;Vittal et al 2005;Filla et al 2006) The syndecans are transmembrane HS proteoglycans that cooperate with specific integrins, bridge to specific cytoskeletal structures, and are involved in inside-out and outside-in signaling. (Couchman and Woods 1999;Couchman et al 2001;Couchman 2003;Yoneda and Couchman 2003) As HS proteoglycans, they can modulate growth factor activity and availability. They are involved in focal adhesions (particularly syndecan-4), stress fiber formation (particularly syndecan-2), cytoskeletal organization and other cellular processes.…”

Section: Cell-surface Ecm Receptors Of the Tmmentioning

confidence: 99%

“…They are involved in focal adhesions (particularly syndecan-4), stress fiber formation (particularly syndecan-2), cytoskeletal organization and other cellular processes. (Couchman and Woods 1999;Couchman et al 2001;Santas et al 2002;Couchman 2003;Yoneda and Couchman 2003;FFilla et al 2004;Peterson et al 2005;Filla et al 2006) Syndecan-4 also appears to localize with the verticies of CLANs and syndecan-2 localizes with podosomes in the TM (Aga, et. al.…”

Section: Cell-surface Ecm Receptors Of the Tmmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

408

443

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The extracellular matrix (ECM) of the trabecular meshwork (TM) is thought to be important in regulating intraocular pressure (IOP) in both normal and glaucomatous eyes. IOP is regulated primarily by a fluid resistance to aqueous humor outflow. However, neither the exact site nor the identity of the normal resistance to aqueous humor outflow has been established. Whether the site and nature of the increased outflow resistance, which is associated with open-angle glaucoma, is the same or different from the normal resistance is also unclear.The ECMs of the TM beams, juxtacanalicular region (JCT) and Schlemm's canal (SC) inner wall are comprised of fibrillar and non-fibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans (GAGs) and proteoglycans. Both basement membranes and stromal ECM are present in the TM beams and JCT region. Cell adhesion proteins, cell surface ECM receptors and associated binding proteins are also present in the beams, JCT and SC inner wall region.The outflow pathway ECM is relatively dynamic, undergoing constant turnover and remodeling. Regulated changes in enzymes responsible for ECM degradation and biosynthetic replacement are observed. IOP homeostasis, triggered by pressure changes or mechanical stretching of the TM, appears to involve ECM turnover. Several cytokines, growth factors and drugs, which affect the outflow resistance, change ECM component expression, mRNA alternative splicing, cellular cytoskeletal organization or all of these. Changes in ECM associated with open-angle glaucoma have been identified.

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“…Syndecan-1 is found predominantly on epithelial cells. It is involved in several cellular processes that rely on interactions with extracellular matrix proteins, growth factors, chemokines and adhesion molecules (Rapraeger, 2000;Couchman, 2003). In myeloma, syndecan-1 has been shown to colocalize with growth factors in the uropods of MMC (Borset et al, 2000), and to promote hepatocyte growth factor (HGF) activity on MMC (Derksen et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

et al. 2006

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The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro.To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-a were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) -neuregulin-1, amphiregulin, HB-EGF -promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10 5 molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy.

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Syndecans: proteoglycan regulators of cell-surface microdomains?

Cited by 382 publications

References 110 publications

Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

Induction of a CXCL8 binding site on endothelial syndecan‐3 in rheumatoid synovium

Extracellular matrix in the trabecular meshwork

Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma

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