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

Snigireva, A. V.; Vrublevskaya, V. V.; Afanasyev, V. N.; Morenkov, O. S.

doi:10.1080/19336918.2015.1103421

Cited by 21 publications

(23 citation statements)

References 40 publications

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“…We therefore attempted to refine the binding site for HSP90α in FN70 by using the ability of the FN30 and FN45 regions to selectively bind heparin and gelatin, respectively. Additionally, HSP90 has previously been shown to bind heparin [59], which allowed us to assess if HSP90 binding to heparin would be competitive with FN70. FN70-transfected cell lysate was added to heparin beads and the level of endogenous HSP90 in the heparin-bound protein complex was determined ( Figure 5A).…”

Section: Fn70 and Hsp90 Interaction In The Presence Of Heparin And Gementioning

confidence: 99%

HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation

Chakraborty

Boel

Edkins

2020

Cells

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Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly. The highest affinity interaction was with the 30-kDa (heparin-binding) FN fragment, which also showed the greatest colocalization in cells and accommodated both HSP90 and heparin in the complex. The strength of interaction with HSP90 was influenced by the inherent stability of the FN fragments, together with the type of motif, where HSP90 preferentially bound the type-I FN repeat over the type-II repeat. Exogenous extracellular HSP90 led to increased incorporation of both full-length and 70-kDa fragments of FN into fibrils. Together, our data suggested that HSP90 may regulate FN matrix assembly through its interaction with N-terminal FN fragments.

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Section: Fn70 and Hsp90 Interaction In The Presence Of Heparin And Gementioning

confidence: 99%

HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation

Chakraborty

Boel

Edkins

2020

Cells

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“…This hypothesis is based on observations that treatment of cells with sodium chlorate, heparinase, and heparin leads to detachment of HSP90 proteins from cell surface and inhibits binding of exogenous HSP90 proteins. 48 Therefore, it is tempting to propose that rLPG3 could also interact with human cells using a similar mechanism.…”

Section: Discussionmentioning

confidence: 99%

Lipophosphoglycan 3 FromLeishmania infantum chagasiBinds Heparin With Micromolar Affinity

Martins

Zeraik

Alves

et al. 2018

Bioinform Biol Insights

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Leishmania infantum chagasi is an intracellular protozoan parasite responsible for visceral leishmaniasis, a fatal disease in humans. Heparin-binding proteins (HBPs) are proteins that bind to carbohydrates present in glycoproteins or glycolipids. Evidence suggests that HBPs present on Leishmania surface participate in the adhesion and invasion of parasites to tissues of both invertebrate and vertebrate hosts. In this study, we identified the product with an HSP90 (heat shock protein 90) domain encoded by lipophosphoglycan (LPG3) gene as a L infantum chagasi HBP (HBPLc). Structural analysis using the LPG3 recombinant protein suggests that it is organized as a tetramer. Binding analysis confirms that it is capable of binding heparin with micromolar affinity. Inhibition of adenosine triphosphatase activity in the presence of heparin, molecular modeling, and in silico docking analysis suggests that heparin-binding site superimposes with the adenosine triphosphate–binding site. Together, these results show new properties of LPG3 and suggest an important role in leishmaniasis.

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“…Heat shock proteins (HSPs) usually locate to the endoplasmic reticulum, mitochondria and cytosol, but have also been found on the cell surface (Bzowska et al 2017;Gonzalez-Gronow et al 2009;Soltys and Gupta 1996). These cell-surface exposed HSPs may be bound to heparan sulphate, which has been demonstrated for HSP90 (Snigireva et al 2015), as they often possess heparin binding activity (Harada et al 2014;Itoh and Tashima 1993;Ménoret and Bell 2000). This assumption was further supported by the high abundance of Calnexin, an endoplasmic reticulum chaperone and lectin, that has been found to associate with cell surface glycoproteins in HeLa cells (Okazaki et al 2000).…”

Section: Membrane Crosslinking Studies Indicate Close Neighbourhood Omentioning

confidence: 99%

A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4

Habeler¹,

Lindner

Redl³

2020

Biological Chemistry

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Lipocalins, small extracellular hydrophobic molecule carriers, can be internalized by a variety of different cells. However, to date receptors have only been identified for human lipocalins. Here, we specifically investigated uptake mechanisms for lipocalins ß-lactoglobulin and Fel d 4 in HeLa and Chinese hamster ovary (CHO) cells. We provide evidence that cell surface heparan sulphate proteoglycan is essential for internalization of these lipocalins. In HeLa cells, lipocalin uptake was inhibited by competition with soluble heparin, enzymatic digestion of cellular heparan sulphate by heparinase and inhibition of its biosynthesis by sodium chlorate. Biochemical studies by heparin affinity chromatography and colocalization studies further supported a role of heparan sulphate proteoglycan in lipocalin uptake. Finally, lipocalin uptake was blocked in CHO mutant cells defective in glycosaminoglycan biosynthesis whereas in wild-type cells it was clearly detectable. Thus, cell surface heparan sulphate proteoglycan represents a novel component absolutely participating in the cellular uptake of some lipocalins.

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

Cited by 21 publications

References 40 publications

HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation

HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation

Lipophosphoglycan 3 FromLeishmania infantum chagasiBinds Heparin With Micromolar Affinity

A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4

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