Endoglycan, a Member of the CD34 Family, Functions as an L-selectin Ligand through Modification with Tyrosine Sulfation and Sialyl Lewis x

Fieger, Claudia; Sassetti, Christopher M.; Rosen, Steven D.

doi:10.1074/jbc.m304204200

Cited by 66 publications

(67 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is intuitive that endoglycan-Ig would form a dimeric bond with P-selectin, because it was constructed by replacing the two Fab legs of a human IgG with two endoglycan extracellular domains (12,26,27). But why did none of the anti-P-selectin mAbs, each of which has two Fab legs, exhibit characteristics of dimeric bonds?…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Stiffness of Selectins

Sarangapani¹,

Marshall

McEver

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

During inflammation, selectin-ligand interactions provide forces for circulating leukocytes to adhere to vascular surfaces, which stretch the interacting molecules, suggesting that mechanical properties may be pertinent to their biological function. From mechanical measurements with atomic force microscopy, we analyzed the molecular characteristics of selectins complexed with ligands and antibodies. Respective stiffness of L-, E-, and P-selectins (4.2, 1.4, and 0.85 piconewton/nm) correlated inversely with the number (2, 6, and 9) of consensus repeats in the selectin structures that acted as springs in series to dominate their compliance. After reconstitution into a lipid bilayer, purified membrane P-selectin remained a dimer, capable of forming dimeric bonds with P-selectin glycoprotein ligand (PSGL)-1, endoglycan-Ig, and a dimeric form of a glycosulfopeptide modeled after the N terminus of PSGL-1. By comparison, purified membrane L-and E-selectin formed only monomeric bonds under identical conditions. Ligands and antibodies were much less stretchable than selectins. The length of endoglycan-Ig was found to be 51 ؎ 12 nm. These results provide a comprehensive characterization of the molecular stiffness of selectins and illustrate how mechanical measurements can be utilized for molecular analysis, e.g. evaluating the multimericity of selectins and determining the molecular length of endoglycan.The physical properties of biomolecules can be exploited as tools for their analysis. For instance, electrophoresis that separates proteins according to mass and charge can be exploited to analyze molecular identity and abundance. Physical properties of many biomolecules also have critical roles in their functions. As an example, bending rigidities of actin and microtubule enable these cytoskeletal proteins to provide mechanical support to the cell. Adhesion molecules are also subjected to forces because they anchor cells to other cells or to the extracellular matrix. Mechanical properties and their relevance to biological function of DNA and muscle proteins (e.g. titin and ubiquitin) have been extensively documented (1-8). However, limited studies exist on the mechanical characterization of adhesion molecules and on the utilization of such mechanical measurements for molecular analysis. Here, we employ atomic force microscopy (AFM) 4 to measure mechanical properties of molecular complexes of selectins and their ligands or monoclonal antibodies (mAbs) and use mechanical measurements to address biological issues involving these molecules.Each of the three selectins consists of an N-terminal lectin domain, an epidermal growth factor (EGF)-like domain, 2, 6, or 9 (for L-, E-or P-selectin, respectively) short consensus repeats (CRs), a transmembrane domain, and a short cytoplasmic tail (Fig. 1A). During inflammation, selectin-ligand interactions mediate tethering and rolling of circulating leukocytes on vascular surfaces under a mechanically stressful milieu (9). These molecular complexes are subjected to physical forces that ...

show abstract

Section: Discussionmentioning

confidence: 99%

“…Mechanical Properties of Endoglycan-Endoglycan is a PSGL-1-like L-selectin ligand of the CD34 family of sialomucins expressed on endothelial cells (12,26,27). Experiments were performed using endoglycan-Ig captured by protein G adsorbed on AFM tips (Fig.…”

Section: Contributions Of Ligands (Or Mabs) To Complexmentioning

confidence: 99%

Molecular Stiffness of Selectins

Sarangapani¹,

Marshall

McEver

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…This remaining L-selectin ligand activity is apparently more than that expected from residual 6-sulfo sLe x present in LSST ⌬ / Core2GlcNAcT ⌬ mice. As shown recently, non-sulfated sLe x on extended core 1 O-glycans serves as an L-selectin ligand, although it is not as good a ligand as sLe x on core 2-branched O-glycans (43)(44)(45). Because LSST ⌬ /Core2GlcNAcT ⌬ mice contain non-sulfated sLe x in 18.7% of total O-glycans, it is likely that non-sulfated sLe x on extended core 1 O-glycans contributes to this remaining L-selectin ligand.…”

Section: Lsstmentioning

confidence: 99%

Core 2 Branching β1,6-N-Acetylglucosaminyltransferase and High Endothelial Venule-restricted Sulfotransferase Collaboratively Control Lymphocyte Homing

Hiraoka

Kawashima

Petryniak

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Lymphocyte recirculation through lymph nodes and Peyer's patches is important for detection of foreign antigens by the immune system and subsequent processes that neutralize these molecules. Lymphocyte recirculation critically depends on interaction between the leukocyte adhesion molecule Lselectin and counterreceptors restricted on specialized post capillary venules, high endothelial venules (HEV) 1 in secondary lymphoid organs. The counterreceptors on the luminal surface of HEV capture circulating lymphocytes via L-selectindependent adhesive interactions that lead, in turn, to lymphocyte tethering and rolling, chemokine-dependent activation, integrin-mediated firm attachment, and lymphocyte transmigration (1-4). L-selectin and its ligands are also implicated in lymphocyte recruitment in certain chronic inflammation. HEVlike microvasculature is induced on endothelium in association with insulitis characteristic of the non-obese diabetic (NOD) mouse and the rejection of heart transplants in rodents and humans (5-8). Similarly, HEV-like structure is observed in inflammatory bowel diseases, rheumatoid arthritis, lymphocytic thyroiditis, and the hyperplastic thymus of the AKR mouse (9 -12). It has been suggested that recruitment of lymphocytes by induced L-selectin ligand may contribute to the pathogenesis of these diseases, which is characteristic of induced HEV-like microvasculature.L-selectin present on leukocytes is a carbohydrate-binding protein characterized by dependence on Ca 2ϩ for its activity. HEVborne L-selectin counterreceptors include GlyCAM-1, CD34, podocalyxin, Sgp200, endoglycan, and MAdCAM-1, all of which have mucin-like domains that act as scaffolding for O-linked oligosaccharides (13). The function of these L-selectin counterreceptors entirely depends on their decoration with specific sialylated, fucosylated, and sulfated oligosaccharides, which contain 6-sulfo sialyl Lewis X (sLe

show abstract

“…Podocalyxin is a member of the CD-34-related family of sialomucins [3][4][5][6][7][8]. Podocalyxin was originally cloned from the human kidney as a component of the podocyte cell glycocalyx, while it was also identified on vascular endothelium and hematopoietic cells [3,4,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Podocalyxin-Targeting Comparative Glycan Profiling Reveals Difference between Human Embryonic Stem Cells and Embryonal Carcinoma Cells

Ikoma¹

2013

J Glycomics Lipidomics

View full text Add to dashboard Cite

Endoglycan, a Member of the CD34 Family, Functions as an L-selectin Ligand through Modification with Tyrosine Sulfation and Sialyl Lewis x

Cited by 66 publications

References 52 publications

Molecular Stiffness of Selectins

Molecular Stiffness of Selectins

Core 2 Branching β1,6-N-Acetylglucosaminyltransferase and High Endothelial Venule-restricted Sulfotransferase Collaboratively Control Lymphocyte Homing

Podocalyxin-Targeting Comparative Glycan Profiling Reveals Difference between Human Embryonic Stem Cells and Embryonal Carcinoma Cells

Contact Info

Product

Resources

About