The role of membrane-bound heat shock Hsp90 proteins in the migration of tumor cells in vitro and the involvement of cell surface heparan sulfate proteoglycans in protein binding to the plasma membrane

BIOPHYSICS ◽  
2016 ◽  
Vol 61 (2) ◽  
pp. 277-283 ◽  
Author(s):  
A. V. Snigireva ◽  
V. V. Vrublevskaya ◽  
Y. Y. Skarga ◽  
O. S. Morenkov
Keyword(s):  
Plasma Membrane ◽  
Heat Shock ◽  
Cell Surface ◽  
Protein Binding ◽  
Heparan Sulfate ◽  
Tumor Cells ◽  
Heparan Sulfate Proteoglycans ◽  
Membrane Bound

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 Cell surface heparan sulfate proteoglycans are involved in the binding of Hsp90α and Hsp90β to the cell plasma membrane

2015 ◽  
Vol 9 (6) ◽  
pp. 460-468 ◽  
Author(s):  
Anastasiya V Snigireva ◽  
Veronika V Vrublevskaya ◽  
Vladimir N Afanasyev ◽  
Oleg S Morenkov
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Cell Plasma Membrane ◽  
Cell Plasma

scholarly journals Morphogenic Effects of Ezrin Require a Phosphorylation-Induced Transition from Oligomers to Monomers at the Plasma Membrane

2000 ◽  
Vol 150 (1) ◽  
pp. 193-204 ◽  
Author(s):  
Alexis Gautreau ◽  
Daniel Louvard ◽  
Monique Arpin
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Wild Type ◽  
Erm Proteins ◽  
Threonine Residue ◽  
Phosphorylation Event ◽  
Membrane Bound

ERM (ezrin, radixin, moesin) proteins act as linkers between the plasma membrane and the actin cytoskeleton. An interaction between their NH2- and COOH-terminal domains occurs intramolecularly in closed monomers and intermolecularly in head-to-tail oligomers. In vitro, phosphorylation of a conserved threonine residue (T567 in ezrin) in the COOH-terminal domain of ERM proteins disrupts this interaction. Here, we have analyzed the role of this phosphorylation event in vivo, by deriving stable clones producing wild-type, T567A, and T567D ezrin from LLC-PK1 epithelial cells. We found that T567A ezrin was poorly associated with the cytoskeleton, but was able to form oligomers. In contrast, T567D ezrin was associated with the cytoskeleton, but its distribution was shifted from oligomers to monomers at the membrane. Moreover, production of T567D ezrin induced the formation of lamellipodia, membrane ruffles, and tufts of microvilli. Both T567A and T567D ezrin affected the development of multicellular epithelial structures. Collectively, these results suggest that phosphorylation of ERM proteins on this conserved threonine regulates the transition from membrane-bound oligomers to active monomers, which induce and are part of actin-rich membrane projections.

scholarly journals Malaria circumsporozoite protein binds to heparan sulfate proteoglycans associated with the surface membrane of hepatocytes.

1993 ◽  
Vol 177 (5) ◽  
pp. 1287-1298 ◽  
Author(s):  
U Frevert ◽  
P Sinnis ◽  
C Cerami ◽  
W Shreffler ◽  
B Takacs ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Target Cell ◽  
Surface Membrane ◽  
Heparan Sulfate Proteoglycans ◽  
Circumsporozoite Protein ◽  
Cell Specificity ◽  
Region Ii

During feeding by infected mosquitoes, malaria sporozoites are injected into the host's bloodstream and enter hepatocytes within minutes. The remarkable target cell specificity of this parasite may be explained by the presence of receptors for the region II-plus of the circumsporozoite protein (CS) on the basolateral domain of the plasma membrane of hepatocytes. We have now identified these receptors as heparan sulfate proteoglycans (HSPG). The binding of CS to the receptors is abolished by heparitinase treatment, indicating that the recognition of region II-plus is via the glycosaminoglycan chains. We have purified and partially characterized the CS-binding HSPGs from HepG2 cells. They have a molecular weight of 400,000-700,000, are tightly associated with the plasma membrane, and are released from the cell surface by very mild trypsinization, a property which the CS receptors share with the syndecan family of proteoglycans.

scholarly journals Syntenin-knock out reduces exosome turnover and viral transduction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rudra Kashyap ◽  
Marielle Balzano ◽  
Benoit Lechat ◽  
Kathleen Lambaerts ◽  
Antonio Luis Egea-Jimenez ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Intercellular Communication ◽  
Scaffold Protein ◽  
Heparan Sulfate Proteoglycans ◽  
Knock Out ◽  
Major Class ◽  
Endosomal Membranes ◽  
Viral Transduction

AbstractExosomal transfers represent an important mode of intercellular communication. Syntenin is a small scaffold protein that, when binding ALIX, can direct endocytosed syndecans and syndecan cargo to budding endosomal membranes, supporting the formation of intraluminal vesicles that compose the source of a major class of exosomes. Syntenin, however, can also support the recycling of these same components to the cell surface. Here, by studying mice and cells with syntenin-knock out, we identify syntenin as part of dedicated machinery that integrates both the production and the uptake of secreted vesicles, supporting viral/exosomal exchanges. This study significantly extends the emerging role of heparan sulfate proteoglycans and syntenin as key components for macromolecular cargo internalization into cells.

Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction

2005 ◽  
Vol 203 (1) ◽  
pp. 166-176 ◽  
Author(s):  
James J. Moon ◽  
Melissa Matsumoto ◽  
Shyam Patel ◽  
Luke Lee ◽  
Jun-Lin Guan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Heparan Sulfate Proteoglycans ◽  
Endothelial Cell Migration

scholarly journals Control of neurotransmitter release and presynaptic plasticity by re-orientation of membrane-bound Munc13-1

2021 ◽  
Author(s):  
Josep Rizo ◽  
Marcial Camacho ◽  
Bradley Quade ◽  
Thorsten Trimbuch ◽  
Junjie Xu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Neurotransmitter Release ◽  
Point Mutations ◽  
Short Term ◽  
In Vitro Reconstitution ◽  
C1 Domain ◽  
Presynaptic Plasticity ◽  
Membrane Bound

Munc13-1 plays a central role in neurotransmitter release through its conserved C-terminal region, which includes a diacyglycerol (DAG)-binding C1 domain, a Ca2+/PIP2-binding C2B domain, a MUN domain and a C2C domain. Munc13-1 was proposed to bridge synaptic vesicles to the plasma membrane in two different orientations mediated by distinct interactions of the C1C2B region with the plasma membrane: i) one involving a polybasic face that yields a perpendicular orientation of Munc13-1 and hinders release; and ii) another involving the DAG-Ca2+-PIP2-binding face that induces a slanted orientation and facilitates release. Here we have tested this model and investigated the role of the C1C2B region in neurotransmitter release. We find that K603E or R769E point mutations in the polybasic face severely impair synaptic vesicle priming in primary murine hippocampal cultures, and Ca2+-independent liposome bridging and fusion in in vitro reconstitution assays. A K720E mutation in the polybasic face and a K706E mutation in the C2B domain Ca2+-binding loops have milder effects in reconstitution assays and do not affect vesicle priming, but enhance or impair Ca2+-evoked release, respectively. The phenotypes caused by combining these mutations are dominated by the K603E and R769E mutations. Our results show that the C1-C2B region of Munc13-1 plays a central role in vesicle priming and support the notion that re-orientation of Munc13-1 controls neurotransmitter release and short-term presynaptic plasticity.

scholarly journals A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate Inhibits the Basal and Hsp90-Stimulated Migration and Invasion of Tumor Cells

2020 ◽  
Vol 11 (2) ◽  
pp. 39 ◽  
Author(s):  
Anastasiya V. Snigireva ◽  
Oleg S. Morenkov ◽  
Yuri Y. Skarga ◽  
Alexander V. Lisov ◽  
Zoya A. Lisova ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cells ◽  
Heat Shock Protein 90 ◽  
Synthetic Polymer ◽  
Heparan Sulfate Proteoglycans ◽  
Migration And Invasion ◽  
Dihydroxybenzoic Acid ◽  
Ht1080 Cells ◽  
Polymeric Conjugate

The extracellular cell surface-associated and soluble heat shock protein 90 (Hsp90) is known to participate in the migration and invasion of tumor cells. Earlier, we demonstrated that plasma membrane-associated heparan sulfate proteoglycans (HSPGs) bind the extracellular Hsp90 and thereby promote the Hsp90-mediated motility of tumor cells. Here, we showed that a conjugate of 2,5-dihydroxybenzoic acid with gelatin (2,5-DHBA–gelatin), a synthetic polymer with heparin-like properties, suppressed the basal (unstimulated) migration and invasion of human glioblastoma A-172 and fibrosarcoma HT1080 cells, which was accompanied by the detachment of a fraction of Hsp90 from cell surface HSPGs. The polymeric conjugate also inhibited the migration/invasion of cells stimulated by exogenous soluble native Hsp90, which correlated with the inhibition of the attachment of soluble Hsp90 to cell surface HSPGs. The action of the 2,5-DHBA–gelatin conjugate on the motility of A-172 and HT1080 cells was similar to that of heparin. The results demonstrate a potential of the 2,5-DHBA–gelatin polymer for the development of antimetastatic drugs targeting cell motility and a possible role of extracellular Hsp90 in the suppression of the migration and invasion of tumor cells mediated by the 2,5-DHBA–gelatin conjugate and heparin.

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