Heparan sulfate proteoglycan and FGF receptor target basic FGF to different intracellular destinations

1993 ◽  
Vol 105 (4) ◽  
pp. 1085-1093 ◽  
Author(s):  
J. Reiland ◽  
A.C. Rapraeger
Keyword(s):  
Heparan Sulfate ◽  
Cellular Responses ◽  
Heparan Sulfate Proteoglycans ◽  
Sulfate Proteoglycan ◽  
Heparin Binding ◽  
Fgf Receptor ◽  
Basic Fgf ◽  
Intracellular Targeting ◽  
Heparin Binding Growth Factors ◽  
Intracellular Fate

Basic FGF is a prototype of a family of heparin binding growth factors that regulate a variety of cellular responses including cell growth, morphogenesis and differentiation. At least two families of receptors bind bFGF and could mediate its response: (1) tyrosine kinase-containing FGF receptors, designated FGFR-1 to FGFR-4, and (2) heparan sulfate proteoglycans that bind bFGF through their heparan sulfate chains. Both are known to undergo internalization and thus bFGF bound to the different receptors may be internalized via more than one pathway. It is not known whether the intracellular fate of bFGF differs depending upon which receptor binds it at the cell surface. To investigate the respective roles of these receptors in the intracellular targeting of bFGF, we utilized NMuMG cells that bind and internalize bFGF through their heparan sulfate proteoglycans, but do not express detectable levels of FGFRs nor respond to bFGF. Basic FGF conjugated to saporin (bFGF-saporin) was used as a probe to study targeting of bFGF by the different receptors. Saporin is a cytotoxin that has no effect on cells if added exogenously. However, it kills cells if it gains access to the cytoplasm. The NMuMG cells internalize bFGF-saporin but are not killed. Transfecting these cells with FGFR-1 results in bFGF-responsive cells, which bind and internalize bFGF through FGFR-1, and are killed. Removing the heparan sulfate from these cells eliminates killing by bFGF-saporin.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Cell-substratum adhesion in chick neural retina depends upon protein-heparan sulfate interactions.

1985 ◽  
Vol 100 (4) ◽  
pp. 1192-1199 ◽  
Author(s):  
G J Cole ◽  
D Schubert ◽  
L Glaser
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Neural Retina ◽  
Heparan Sulfate Proteoglycan ◽  
Retinal Cell ◽  
Sulfate Proteoglycan ◽  
Heparin Binding ◽  
Embryonic Chick ◽  
Retinal Cells ◽  
Inert Surfaces

Embryonic chick neural retina cells in culture release complexes of proteins and glycosaminoglycans, termed adherons, which stimulate cell-substratum adhesion when adsorbed to nonadhesive surfaces. Two distinct retinal cell surface macromolecules, a 170,000-mol-wt glycoprotein and a heparan sulfate proteoglycan; are components of adherons that can independently promote adhesion when coated on inert surfaces. The 170,000-mol-wt polypeptide contains a heparin-binding domain, as indicated by its retention on heparin-agarose columns and its ability to bind [3H]heparin in solution. The attachment of embryonic chick retinal cells to the 170,000-mol-wt protein also depends upon interactions between the protein and the heparan sulfate proteoglycan, since heparan sulfate in solution disrupts adhesion of chick neural retina cells to glass surfaces coated with the 170,000-mol-wt protein. This adhesion is not impaired by chondroitin sulfate or hyaluronic acid, which indicates that inhibition by heparan sulfate is specific. Polyclonal antisera directed against the cell surface heparan sulfate proteoglycan also inhibit attachment of retinal cells to the 170,000-mol-wt protein, which suggests that cell-adheron binding is mediated in part by interactions between cell surface heparan sulfate proteoglycan and 170,000-mol-wt protein contained in the adheron particles. Previous studies have indicated that this type of cell-substratum adhesion is tissue-specific since retina cells do not attach to muscle adherons. Schubert D., M. LaCorbiere, F. G. Klier, and C. Birdwell, 1983, J. Cell Biol. 96:990-998.

scholarly journals Interaction of an Outer Membrane Protein of Enterotoxigenic Escherichia coli with Cell Surface Heparan Sulfate Proteoglycans

2002 ◽  
Vol 70 (3) ◽  
pp. 1530-1537 ◽  
Author(s):  
James M. Fleckenstein ◽  
James T. Holland ◽  
David L. Hasty
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Eukaryotic Cells ◽  
Heparin Binding ◽  
Wild Type ◽  
E Coli

ABSTRACT We have previously shown that enterotoxigenic invasion protein A (Tia), a 25-kDa outer membrane protein encoded on an apparent pathogenicity island of enterotoxigenic Escherichia coli (ETEC) strain H10407, mediates attachment to and invasion into cultured human gastrointestinal epithelial cells. The epithelial cell receptor(s) for Tia has not been identified. Here we show that Tia interacts with cell surface heparan sulfate proteoglycans. Recombinant E. coli expressing Tia mediated invasion into wild-type epithelial cell lines but not invasion into proteoglycan-deficient cells. Furthermore, wild-type eukaryotic cells, but not proteoglycan-deficient eukaryotic cells, attached to immobilized polyhistidine-tagged recombinant Tia (rTia). Binding of epithelial cells to immobilized rTia was inhibited by exogenous heparan sulfate glycosaminoglycans but not by hyaluronic acid, dermatan sulfate, or chondroitin sulfate. Similarly, pretreatment of eukaryotic cells with heparinase I, but not pretreatment of eukaryotic cells with chrondroitinase ABC, inhibited attachment to rTia. In addition, we also observed heparin binding to both immobilized rTia and recombinant E. coli expressing Tia. Heparin binding was inhibited by a synthetic peptide representing a surface loop of Tia, as well as by antibodies directed against this peptide. Additional studies indicated that Tia, as a prokaryotic heparin binding protein, may also interact via sulfated proteoglycan molecular bridges with a number of mammalian heparan sulfate binding proteins. These findings suggest that the binding of Tia to host epithelial cells is mediated at least in part through heparan sulfate proteoglycans and that ETEC belongs on the growing list of pathogens that utilize these ubiquitous cell surface molecules as receptors.

scholarly journals A heparin-binding activity on Leishmania amastigotes which mediates adhesion to cellular proteoglycans.

1993 ◽  
Vol 123 (3) ◽  
pp. 759-766 ◽  
Author(s):  
D C Love ◽  
J D Esko ◽  
D M Mosser
Keyword(s):  
Heparan Sulfate ◽  
Cho Cells ◽  
Mammalian Cells ◽  
Binding Activity ◽  
Heparan Sulfate Proteoglycans ◽  
Heparin Binding ◽  
Wild Type ◽  
Amastigote Form ◽  
High Affinity ◽  
Leishmania Amastigotes

The intracellular amastigote form of leishmania is responsible for the cell-to-cell spread of leishmania infection in the mammalian host. In this report, we identify a high-affinity, heparin-binding activity on the surface of the amastigote form of leishmania. Amastigotes of Leishmania amazonensis bound approximately 120,000 molecules of heparin per cell, with a Kd of 8.8 x 10(-8) M. This heparin-binding activity mediates the adhesion of amastigotes to mammalian cells via heparan sulfate proteoglycans, which are expressed on the surface of mammalian cells. Amastigotes bound efficiently to a variety of adherent cells which express cell-surface proteoglycans. Unlike wild-type CHO cells, which bound amastigotes avidly, CHO cells with genetic deficiencies in heparan sulfate proteoglycan biosynthesis or cells treated with heparitinase failed to bind amastigotes even at high parasite-input dosages. Cells which express normal levels of undersulfated heparan bound amastigotes nearly as efficiently as did wild-type cells. The adhesion of amastigotes to wild-type nonmyeloid cells was almost completely inhibited by the addition of micromolar amounts of soluble heparin or heparan sulfate but not by the addition of other sulfated polysaccharides.l Binding of amastigotes to macrophages, however, was inhibited by only 60% after pretreatment of amastigotes with heparin, suggesting that macrophages have an additional mechanism for recognizing amastigotes. These results suggest that leishmania amastigotes express a high-affinity, heparin-binding activity on their surface which can interact with heparan sulfate proteoglycans on mammalian cells. This interaction may represent an important first step in the invasion of host cells by amastigotes.

Heparinoids and cellular interactions in the vascular system

1996 ◽  
Vol 16 (01) ◽  
pp. 28-34
Author(s):  
K. T. Preissner
Keyword(s):  
Heparan Sulfate ◽  
Vascular System ◽  
Vascular Diseases ◽  
Basement Membranes ◽  
Heparan Sulfate Proteoglycans ◽  
The Body ◽  
Pharmacological Intervention ◽  
Cellular Interactions ◽  
Heparin Binding ◽  
Core Proteins

SummaryHeparin and related polysaccharides have long been used for therapautic intervention in different disease states related to thromboembolic complications. The localization and functional availability of heparin-like components in the body is mostly confined to cell surfaces and extracellular matrix/basement membranes. Their strategic position particularly in the vascular system enables heparinoids linked to various core proteins (designated as heparan sulfate proteoglycans) to interact with a variety of heparin-binding proteins such as apolipoproteins, lipases, proteases and protease inhibitors, matrix proteins as well as surface receptors on other cells and microorganisms. The variety in gene expression of respective core proteins and differences in glycosaminoglycan side chains are relevant factors for the selectivity of these interactions. Heparinoid-associated core proteins serve as co-receptors for a number of metabolic properties of vascular cells as well as for the regulation of cellular processes, particular as they relate to cell growth and differentiation in angiogenesis. Moreover, heparan sulfate proteoglycans contribute to the process of lipoprotein retention in the vessel wall and the onset of atherosclerosis. Elucidation of molecular properties, functions and their role in vascular diseases can lead to valuable information for the design of heparinoid analogues to be used for pharmacological intervention.

Developing Heparan Sulfate Proteoglycan Miniaturized Capillary Column to Study its Recognition Mechanism with its Molecular Target. Application to Human Telomerase, a Cell Penetrating Peptide and Mitoxantrone a Potential Covid-19 Inhibitor.

2021 ◽  
Author(s):  
Yves Claude Guillaume ◽  
CLAIRE ANDRE
Keyword(s):  
Heparan Sulfate ◽  
Capillary Column ◽  
Molecular Target ◽  
Heparan Sulfate Proteoglycans ◽  
Cell Penetrating Peptide ◽  
Sulfate Proteoglycan ◽  
Recognition Mechanism ◽  
A Cell ◽  
Human Telomerase ◽  
Viral Receptors

The interactions of Heparan Sulfate proteoglycans (HSPGs) present on cell surface with target proteins lead to cell signaling and is considered as viral receptors. The analysis of the recognition mechanism...

scholarly journals Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin triggering and its mediated adhesion to endothelial cells.

1996 ◽  
Vol 184 (5) ◽  
pp. 1987-1997 ◽  
Author(s):  
Y Tanaka ◽  
K Kimata ◽  
A Wake ◽  
S Mine ◽  
I Morimoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycan ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Proteoglycan Synthesis ◽  
Sulfate Proteoglycan ◽  
Heparin Binding

Leukocyte migration from circulation into tissue depends on leukocyte integrin-mediated adhesion to endothelium, but integrins cannot function until activated. However, it remains to be understood how tumor cells adhere to endothelium and infiltrate into underlying tissue. We studied mechanisms of extravasation of leukemic cells using adult T cell leukemia (ATL) cells and report the following novel features of cell surface heparan sulfate proteoglycan on ATL cells in ATL cell adhesion to endothelium: ATL cells adhere to endothelial cells through already activated integrins without exogenous stimulation; different from any other hematopoietic cells, ATL cells express a characteristic heparan sulfate capable of immobilizing heparin-binding chemokine macrophage inflammatory protein (MIP)-1 beta, a potent T cell integrin trigger, produced by the cells themselves; competitive interruption of endogenous heparan sulfate proteoglycan synthesis reduces cell surface MIP-1 beta and prevents ATL cells from integrin-mediated adhesion to endothelial cells or intercellular adhesion molecule-1 triggered through G-protein. We propose that leukemic cells adhere to endothelial cells through the adhesion cascade, similar to normal leukocyte, and that the cell surface heparan sulfate, particularly on ATL cells, is pivotally involved in chemokine-dependent autocrine stimulation of integrin triggering by immobilizing the chemokine on them.

scholarly journals Oligomeric self-association of basic fibroblast growth factor in the absence of heparin-like glycosaminoglycans

1999 ◽  
Vol 341 (3) ◽  
pp. 613-620 ◽  
Author(s):  
Joseph C. DAVIS ◽  
Ganesh VENKATARAMAN ◽  
Zachary SHRIVER ◽  
P. Antony RAJ ◽  
Ram SASISEKHARAN
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Heparin Binding ◽  
Fgf Receptor ◽  
Natural Tendency ◽  
Heparin Binding Growth Factors ◽  
Self Association

Basic fibroblast growth factor (FGF-2) represents a class of heparin-binding growth factors that are stored in the extracellular matrix attached to heparin-like glycosaminoglycans (HLGAGs). It has been proposed that cell surface HLGAGs have a central role in the biological activity of FGF-2, presumably by inducing dimers or oligomers of FGF-2 and leading to the dimerization or oligomerization of FGF receptor and hence signal transduction. We have previously proposed that FGF-2 possesses a natural tendency to self-associate to form FGF-2 dimers and oligomers; HLGAGs would enhance FGF-2 self-association. Here, through a combination of spectroscopic, chemical cross-linking and spectrometric techniques, we provide direct evidence for the self-association of FGF-2 in the absence of HLGAGs, defying the notion that HLGAGs induce FGF-2 oligomerization. Further, the addition of HLGAGs seems to enhance significantly the FGF-2 oligomerization process without affecting the relative percentages of FGF-2 dimers, trimers or oligomers. FGF-2 self-association is consistent with FGF-2's possessing biological activity both in the presence and in the absence of HLGAGs; this leads us to propose that FGF-2 self-association enables FGF-2 to signal both in the presence and in the absence of HLGAGs.

Topical secretoneurin gene therapy accelerates diabetic wound healing by interaction between heparan-sulfate proteoglycans and basic FGF

Angiogenesis ◽  
2013 ◽  
Vol 17 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Karin Albrecht-Schgoer ◽  
Wilfried Schgoer ◽  
Markus Theurl ◽  
Ursula Stanzl ◽  
Daniela Lener ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Wound Healing ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Diabetic Wound ◽  
Basic Fgf ◽  
Diabetic Wound Healing

scholarly journals Molecular Characterization of the Heparin-Dependent Transduction Domain on the Capsid of a Novel Adeno-Associated Virus Isolate, AAV(VR-942)

2008 ◽  
Vol 82 (17) ◽  
pp. 8911-8916 ◽  
Author(s):  
Michael Schmidt ◽  
Lakshmanan Govindasamy ◽  
Sandra Afione ◽  
Nick Kaludov ◽  
Mavis Agbandje-McKenna ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Virus Isolate ◽  
Simian Virus ◽  
Complementation Group ◽  
Heparan Sulfate Proteoglycans ◽  
Sulfate Proteoglycan ◽  
Amino Acid Residues ◽  
Adeno Associated Virus ◽  
High Level

ABSTRACT A new adeno-associated virus (AAV), referred to as AAV(VR-942), has been isolated as a contaminant of adenovirus strain simian virus 17. The sequence of the rep gene places it in the AAV serotype 2 (AAV2) complementation group, while the capsid is only 88% identical to that of AAV2. High-level AAV(VR-942) transduction activity requires cell surface heparan sulfate proteoglycans, although AAV(VR-942) lacks residues equivalent to the AAV2 R585 and R588 amino acid residues essential for mediating the interaction of AAV2 with the heparan sulfate proteoglycan receptor. Instead, AAV(VR-942) uses a distinct transduction region. This finding shows that distinct domains on different AAV isolates can be responsible for the same activities.

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