scholarly journals Constitutive Release of α4 Type V Collagen N-terminal Domain by Schwann Cells and Binding to Cell Surface and Extracellular Matrix Heparan Sulfate Proteoglycans

2004 ◽  
Vol 279 (49) ◽  
pp. 51282-51288 ◽  
Author(s):  
Katrina Rothblum ◽  
Richard C. Stahl ◽  
David J. Carey
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Schwann Cells ◽  
Heparan Sulfate Proteoglycans ◽  
Type V Collagen ◽  
Terminal Domain ◽  
Type V

scholarly journals Membrane anchoring of heparan sulfate proteoglycans by phosphatidylinositol and kinetics of synthesis of peripheral and detergent-solubilized proteoglycans in Schwann cells.

1989 ◽  
Vol 108 (5) ◽  
pp. 1891-1897 ◽  
Author(s):  
D J Carey ◽  
D M Evans
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Schwann Cells ◽  
Electrostatic Interactions ◽  
Heparan Sulfate Proteoglycans ◽  
Membrane Bound ◽  
Covalently Linked ◽  
Mode Of Attachment ◽  
Membrane Anchoring ◽  
Kinetics Of

Previous studies have shown that Schwann cells synthesize both peripheral and integral hydrophobic cell surface heparan sulfate proteoglycans (HSPGs). The experiments reported here were undertaken to investigate the mode of attachment of these proteins to the cell surface and their potential interrelationship. The binding of the hydrophobic HSPGs to membranes appears to be via covalently linked phosphatidylinositol based on the observation that incubation of the detergent-solubilized protein with purified phosphatidylinositol-specific phospholipase C significantly reduces the ability of the HSPGs to associate with phospholipid vesicles in a reconstitution assay. The peripherally associated HSPGs were released from the cells by incubation in the presence of heparin (10 mg/ml), 10 mM phytic acid (inositol hexaphosphate), or 2 M NaCl. These treatments also solubilized basement membrane HSPGs synthesized by the Schwann cells. These data suggest that the peripheral HSPGs are bound to the surface by electrostatic interactions. The peripheral and hydrophobic HSPGs were identical in overall size, net charge, length of glycosaminoglycan chains, and patterns of N-sulfation. To determine whether the peripheral HSPGs were derived from the membrane-bound form by cleavage of the membrane anchor, we examined the kinetics of synthesis and degradation of the two forms of HSPGs. The results obtained indicated the existence of two pools of detergent-solubilized HSPG with fast (t1/2 = 6 h) and slow (t1/2 = 55 h) turnover kinetics. The data were consistent with a model in which the peripheral HSPGs were derived from the slowly turning over pool of detergent-solubilized HSPGs.

scholarly journals Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias?

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 596 ◽  
Author(s):  
Cagno ◽  
Tseligka ◽  
Jones ◽  
Tapparel
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Blood Coagulation ◽  
Biological Activities ◽  
Extracellular Matrix Proteins ◽  
Heparan Sulfate Proteoglycans ◽  
Matrix Proteins ◽  
Cell Homeostasis ◽  
Viral Attachment

Heparan sulfate proteoglycans (HSPG) are composed of unbranched, negatively charged heparan sulfate (HS) polysaccharides attached to a variety of cell surface or extracellular matrix proteins. Widely expressed, they mediate many biological activities, including angiogenesis, blood coagulation, developmental processes, and cell homeostasis. HSPG are highly sulfated and broadly used by a range of pathogens, especially viruses, to attach to the cell surface.

scholarly journals Schwann Cell Adhesion to a Novel Heparan Sulfate Binding Site in the N-terminal Domain of α4 Type V Collagen Is Mediated by Syndecan-3

2001 ◽  
Vol 277 (9) ◽  
pp. 7619-7625 ◽  
Author(s):  
Robert Erdman ◽  
Richard C. Stahl ◽  
Katrina Rothblum ◽  
Michael A. Chernousov ◽  
David J. Carey
Keyword(s):  
Cell Adhesion ◽  
Schwann Cell ◽  
Heparan Sulfate ◽  
Binding Site ◽  
Type V Collagen ◽  
Terminal Domain ◽  
Type V

scholarly journals Relationship of heparan sulfate proteoglycans to the cytoskeleton and extracellular matrix of cultured fibroblasts.

1984 ◽  
Vol 99 (5) ◽  
pp. 1743-1753 ◽  
Author(s):  
A Woods ◽  
M Höök ◽  
L Kjellén ◽  
C G Smith ◽  
D A Rees
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Focal Adhesions ◽  
Dermal Fibroblasts ◽  
Heparan Sulfate Proteoglycans ◽  
Immunofluorescent Staining ◽  
Rat Embryo ◽  
Double Labeling ◽  
Cultured Fibroblasts

The distribution of heparan sulfate proteoglycans (HSPG) on cultured fibroblasts was monitored using an antiserum raised against cell surface HSPG from rat liver. After seeding, HSPG was detected by immunofluorescence first on cell surfaces and later in fibrillar deposits of an extracellular matrix. Cell surface HSPG aligned with microfilament bundles of rat embryo fibroblasts seen by phase-contrast microscopy but was diffuse on transformed rat dermal fibroblasts (16C cells) which lack obvious stress fibers. Focal adhesions isolated from either cell type and monitored by interference reflection microscopy showed a concentration of HSPG labeling with respect to the rest of the membrane. Increased labeling in these areas was also seen for fibronectin (FN) by using an antiserum that detects both plasma and cell-derived FN. Double immunofluorescent staining of fully adherent rat embryo fibroblast cells showed some co-distribution of HSPG and FN, and this was confirmed by immunoelectron microscopy, which detected HSPG at localized areas of dorsal and ventral cell membranes, overlapping cell margins, and in the extracellular matrix. During cell shape changes on rounding and spreading, HSPG and FN may not co-distribute. Double labeling for actin and either HSPG or FN showed a closer correlation of actin with HSPG than with FN. The studies are consistent with HSPG being closely involved in a transmembrane cytoskeletal-matrix interaction; the possibility that HSPG coordinates the deposition of FN and other matrix components with cytoskeletal organization is discussed.

scholarly journals Binding of heparan sulfate to type V collagen

1989 ◽  
Vol 264 (14) ◽  
pp. 7950-7956 ◽  
Author(s):  
R G LeBaron ◽  
A Höök ◽  
J D Esko ◽  
S Gay ◽  
M Höök
Keyword(s):  
Heparan Sulfate ◽  
Type V Collagen ◽  
Type V

scholarly journals Distinct glycosaminoglycan chain length and sulfation patterns required for cellular uptake of Tau, Aβ, and α-Synuclein

2017 ◽  
Author(s):  
Barbara E. Stopschinski ◽  
Brandon B. Holmes ◽  
Gregory M. Miller ◽  
Jaime Vaquer-Alicea ◽  
Linda C. Hsieh-Wilson ◽  
...  
Keyword(s):  
Cell Surface ◽  
Neurodegenerative Diseases ◽  
Heparan Sulfate ◽  
Chain Length ◽  
Cellular Uptake ◽  
Genetic Manipulation ◽  
Heparan Sulfate Proteoglycans ◽  
Cell Uptake ◽  
Major Genes

AbstractTranscellular propagation of aggregate “seeds” has been proposed to mediate progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We have previously determined that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface. This mediates uptake and intracellular seeding. The specificity and mode of binding to HSPGs has been unknown. We used modified heparins to determine the size and sulfation requirements of glycosaminoglycan (GAGs) binding to aggregates in biochemical and cell uptake and seeding assays. Aggregates of tau require a precise GAG architecture with defined sulfate moieties in the N- and 6-O-positions, whereas α-synuclein and Aβ rely slightly more on overall charge on the GAGs. To determine the genetic requirements for aggregate uptake, we individually knocked out the major genes of the HSPG synthesis pathway using CRISPR/Cas9 in HEK293T cells. Knockout of EXT1, EXT2 and EXTL3, N-sulfotransferase (NDST1), and 6-O-sulfotransferase (HS6ST2) significantly reduced tau uptake. α-Synuclein was not sensitive to HS6ST2 knockout. Good correlation between pharmacologic and genetic manipulation of GAG binding by tau and α-synuclein indicates specificity that may help elucidate a path to mechanism-based inhibition of transcellular propagation of pathology.

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