scholarly journals Targeting heparin and heparan sulfate protein interactions

2017 ◽  
Vol 15 (27) ◽  
pp. 5656-5668 ◽  
Author(s):  
Ryan J. Weiss ◽  
Jeffrey D. Esko ◽  
Yitzhak Tor
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Protein Interactions ◽  
Human Disease ◽  
Binding Proteins ◽  
Cellular Functions ◽  
Animal Cells ◽  
Carbohydrate Chains

Heparan sulfate is ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These negatively-charged carbohydrate chains play essential roles in many important cellular functions by interacting with various heparan sulfate binding proteins (HSBP). This review discusses methods for targeting these complex biomolecules, as strategies for treating human disease.

Surface Structure of Nucleated Animal Cells: Carbon Replicas

1967 ◽  
Vol 25 ◽  
pp. 120-121
Author(s):  
Robert M. Glaeser ◽  
Thea B. Scott
Keyword(s):  
Cell Surface ◽  
Surface Structure ◽  
Particle Diameter ◽  
Cellular Functions ◽  
Animal Cells ◽  
Replica Technique ◽  
Carbon Replica ◽  
Characteristic Particle ◽  
Cell Surface Structure ◽  
Carbon Replicas

The carbon-replica technique can be used to obtain information about cell-surface structure that cannot ordinarily be obtained by thin-section techniques. Mammalian erythrocytes have been studied by the replica technique and they appear to be characterized by a pebbly or “plaqued“ surface texture. The characteristic “particle” diameter is about 200 Å to 400 Å. We have now extended our observations on cell-surface structure to chicken and frog erythrocytes, which possess a broad range of cellular functions, and to normal rat lymphocytes and mouse ascites tumor cells, which are capable of cell division. In these experiments fresh cells were washed in Eagle's Minimum Essential Medium Salt Solution (for suspension cultures) and one volume of a 10% cell suspension was added to one volume of 2% OsO4 or 5% gluteraldehyde in 0.067 M phosphate buffer, pH 7.3. Carbon replicas were obtained by a technique similar to that employed by Glaeser et al. Figure 1 shows an electron micrograph of a carbon replica made from a chicken erythrocyte, and Figure 2 shows an enlarged portion of the same cell.

scholarly journals High affinity immunoreactive FGF receptors in the extracellular matrix of vascular endothelial cells--implications for the modulation of FGF-2.

1995 ◽  
Vol 128 (6) ◽  
pp. 1221-1228 ◽  
Author(s):  
A Hanneken ◽  
P A Maher ◽  
A Baird
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Protein Interactions ◽  
Binding Proteins ◽  
Vascular Endothelial Cells ◽  
Extracellular Domain ◽  
Cytoplasmic Domain ◽  
Basement Membranes ◽  
Vascular Endothelial ◽  
High Affinity

We recently characterized three FGF-binding proteins (FGF-BPs) which are soluble forms of the extracellular domains of the high affinity FGF receptors (Hanneken, A. M., W. Ying, N. Ling, and A. Baird. Proc. Natl. Acad. Sci. USA. 1994. 91:9170-9174). These proteins circulate in blood and have been proposed to modulate the biological activity of the FGF family of proteins. Immunohistochemical studies now demonstrate that these soluble, truncated FGF receptors are also present in the basement membranes of retinal vascular endothelial cells. These immunoreactive proteins can be detected with antibodies raised to the extracellular domain of FGFR-1 but not with antibodies raised to either the juxtamembrane domain or the cytoplasmic domain of FGFR-1. Western blotting of human retinal extracts with the antibody raised to the extracellular domain of FGFR-1 detects specific, low molecular mass proteins at 85 kD and 55 kD, corresponding in size to the FGF-BPs, which are not detected with antibodies against the cytoplasmic domain of the receptor. The interaction of this receptor with the extracellular matrix is not dependent on the presence of FGF-2. Immunoreactive receptors are still detected in vascular basement membranes after the removal of FGF-2 with heparitinase. In addition, the recombinant extracellular domain of FGFR-1 continues to bind to corneal endothelial cell matrix after endogenous FGF-2 has been removed with 2 M NaCl. Acid treatment, which has been shown to disrupt protein interactions with the extracellular matrix, leads to a significant reduction in the presence of the matrix form of the FGF receptor. This loss can be restored with exogenous incubations of the recombinant extracellular domain of FGFR-1. This report is the first demonstration that a truncated form of a high affinity growth factor receptor can be localized to the extracellular matrix. These findings add to the list of binding proteins associated with the extracellular matrix (IGFBP-5) and suggest a potentially new regulatory mechanism for controlling the biological availability of FGF, and other peptide growth factors, in the extracellular matrix.

scholarly journals Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

2009 ◽  
Vol 81 (3) ◽  
pp. 409-429 ◽  
Author(s):  
Juliana L. Dreyfuss ◽  
Caio V. Regatieri ◽  
Thais R. Jarrouge ◽  
Renan P. Cavalheiro ◽  
Lucia O. Sampaio ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Signaling ◽  
Heparan Sulfate ◽  
Protein Interactions ◽  
Cellular Signaling ◽  
Structural Characteristics ◽  
Heparan Sulfate Proteoglycans ◽  
Protein Motifs ◽  
Extracellular Matrix Components ◽  
Heparan Sulfates

Heparan sulfate proteoglycans are ubiquitously found at the cell surface and extracellular matrix in all the animal species. This review will focus on the structural characteristics of the heparan sulfate proteoglycans related to protein interactions leading to cell signaling. The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation. The role of the heparan sulfate proteoglycans in cellular signaling and endocytic uptake pathways is also discussed.

Alveolar type II cells synthesize hydrophobic cell-associated proteoglycans with multiple core proteins

1992 ◽  
Vol 263 (3) ◽  
pp. L348-L356 ◽  
Author(s):  
W. M. Maniscalco ◽  
M. H. Campbell
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Core Protein ◽  
Primary Cultures ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Core Proteins

Type II alveolar epithelial cells interact with the extracellular matrix via cell surface receptors for matrix ligands. Cell surface proteoglycans, which are hydrophobic due to their membrane insertion domains, are one of several classes of molecules that may be receptors for matrix ligands. To analyze the hydrophobic proteoglycans synthesized by adult alveolar type II cells, we labeled these cells with 35SO4 and [3H]leucine in short-term primary cultures. Cell-associated hydrophobic proteoglycans and culture medium-derived proteoglycans were purified and characterized. Both the hydrophobic proteoglycans and medium-derived proteoglycans, which were not hydrophobic, had mainly heparan sulfate glycosaminoglycans. Analysis of core proteins of the hydrophobic proteoglycans showed three proteins, 47, 65, and 90 kDa. The 47- and 65-kDa core proteins were substituted only with heparan sulfate chains. The 90-kDa core protein was seen only after digestion with both heparitinase and chondroitin ABC lyase, suggesting it was a hybrid having both heparan sulfate and chondroitin-dermatan sulfate chains. These findings were confirmed by iodination of the core proteins. The hydrophobic cell-associated proteoglycans inserted into artificial liposomes, whereas the medium-derived molecules did not. These data document heterogeneity in core protein and glycosaminoglycan chains among hydrophobic proteoglycans synthesized in vitro by adult alveolar type II cells. These molecules may have diverse functions in regulating type II cell interaction with the extracellular matrix.

scholarly journals Cell Surface Localization of Heparanase on Macrophages Regulates Degradation of Extracellular Matrix Heparan Sulfate

2004 ◽  
Vol 172 (6) ◽  
pp. 3830-3835 ◽  
Author(s):  
Norihiko Sasaki ◽  
Nobuaki Higashi ◽  
Tomohiro Taka ◽  
Motowo Nakajima ◽  
Tatsuro Irimura
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Surface Localization ◽  
Cell Surface Localization

scholarly journals The heparan sulfate and its diverse biological activities

2014 ◽  
Vol 27 (4) ◽  
pp. 209-212
Author(s):  
Iwona Kaznowska-Bystryk
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Biological Function ◽  
Molecular Level ◽  
Biological Activities ◽  
Therapeutic Strategies ◽  
Detailed Knowledge ◽  
And Storage

Abstract Heparan sulfate (HS) is one of the most common glycosaminoglycan (GAG) in mammals. It is composed of relatively simple disaccharide subunits, which, by further modification, such as sulfation and epimerization, potentially offer huge diversity in biological function. GAG chains of different length, different patterns of sulfation, and other modifications, depending on location, generate unique forms. Due to polyanion charges, these compounds can interact with other molecules, such as proteins, cytokines, chemokines and growth factors, both on the cell surface and inside the extracellular matrix. These interactions serve protective and storage functions for the compounds, safeguarding them from proteolysis. In this way, HS is involved in numerous signaling pathways, and in growth and differentiation processes. Disrupted interactions between the HS and growth factors, cytokines or other proteins have been observed in various disorders, among these Alzheimer’s disease, epilepsy, atherosclerosis, diabetes, and cancer processes. Detailed knowledge of these relationships at the molecular level will allow researchers to understand the mechanisms underlying these disorders and enable the development of effective therapeutic strategies.

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