Sialidase Treatment Exposes the βT1-Integrin Active Ligand Binding Site on HL60 Cells and Increases Binding to Fibronectin

Pretzlaff, Robert K.; Xue, Vivian Weiwen; Rowin, Mark E.

doi:10.3109/15419060009040306

Cited by 46 publications

(36 citation statements)

References 46 publications

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“…Biochemical engineering of the side chain of sialic acid might activate ␤1-integrins. It has been shown that ␤1-integrins can be activated by removal of sialic acid; treatment with sialidases increases the adhesion of HL60 cells to fibronectin (Pretzlaff et al, 2000). This activation might be one explanation for the specific stimulation of neurite outgrowth on laminin induced by ManNProp treatment.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

et al. 2002

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Sialylation is essential for development and regeneration in mammals. Using N-propanoylmannosamine, a novel precursor of sialic acid, we were able to incorporate unnatural sialic acids with a prolonged N-acyl side chain (e.g., N-propanoylneuraminic acid) into cell surface glycoconjugates. Here we report that this biochemical engineering of sialic acid leads to a stimulation of neuronal cells. Both PC12 cells and cerebellar neurons showed a significant increase in neurite outgrowth after treatment with this novel sialic acid precursor. Furthermore, also the reestablishment of the perforant pathway was stimulated in brain slices. In addition, we surprisingly identified several cytosolic proteins with regulatory functions, which are differentially expressed after treatment with N-propanoylmannosamine. Because sialic acid is the only monosaccharide that is activated in the nucleus, we hypothesize that transcription could be modulated by the unnatural CMP-Npropanoylneuraminic acid and that sialic acid activation might be a general tool to regulate cellular functions, such as neurite outgrowth.

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Section: Discussionmentioning

confidence: 99%

Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

et al. 2002

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“…In one study, the enzymatic removal of sialic acid residues from the surface of HL60 cells stimulated cell adhesion to fibronectin (19). This enhanced binding was thought to be due to altered activity of the ␤ 1 integrin, because ␤ 1 integrins from sialidase-treated cells expressed elevated levels of a ␤ 1 -specific activation epitope.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence suggests that, in hematopoietic cells, sialylation of cell surface receptors is inversely correlated with cell adhesion to extracellular matrix ligands (13,19,31), although this has not been universally observed (14). In one study, the enzymatic removal of sialic acid residues from the surface of HL60 cells stimulated cell adhesion to fibronectin (19).…”

Section: Discussionmentioning

confidence: 99%

“…Desialylated, Purified ␣ 5 ␤ 1 Integrins Demonstrate Enhanced Fibronectin Binding-Previous studies have shown that the enzymatic removal of sialic acids from the cell surface can modulate cell adhesion to extracellular matrix ligands (19,20). However, because multiple cell surface receptors are likely to be affected by the desialylating enzyme, it is not currently clear FIG.…”

Section: Inhibiting the Expression Of Hyposialylated ␤ 1 Integrins Blmentioning

confidence: 99%

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Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors

Semel

Seales

Singhal

et al. 2002

Journal of Biological Chemistry

102

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Despite numerous reports suggesting that ␤ 1 integrin receptors undergo differential glycosylation, the potential role of N-linked carbohydrates in modulating integrin function has been largely ignored. In the present study, we find that ␤ 1 integrins are differentially glycosylated during phorbol ester (PMA)-stimulated differentiation of myeloid cells along the monocyte/macrophage lineage. PMA treatment of two myeloid cell lines, U937 and THP-1, induces a down-regulation in expression of the ST6Gal I sialyltransferase. Correspondingly, the ␤ 1 integrin subunit becomes hyposialylated, suggesting that the ␤ 1 integrin is a substrate for this enzyme. The expression of hyposialylated ␤ 1 integrin isoforms is temporally correlated with enhanced binding of myeloid cells to fibronectin, and, importantly, fibronectin binding is inhibited when the Golgi disrupter, brefeldin A, is used to block the expression of the hyposialylated form. Consistent with the observation that cells with hyposialylated integrins are more adhesive to fibronectin, we demonstrate that the enzymatic removal of sialic acid residues from purified ␣ 5 ␤ 1 integrins stimulates fibronectin binding by these integrins. These data support the hypothesis that unsialylated ␤ 1 integrins are more adhesive to fibronectin, although desialylation of ␣ 5 subunits could also contribute to increased fibronectin binding. Collectively our results suggest a novel mechanism for regulation of the ␤ 1 integrin family of cell adhesion receptors.

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“…To date, the contribution of N-glycosylation to modulation of the a4b1 integrin function, in the presence of terminal SA residues, is not understood fully. Recent reports suggest that hyposialylation of integrins enhances binding of the integrin to fibronectin by exposing the active ligand-binding site to the ligand (Pretzlaff et al, 2000;Semel et al, 2002). Further studies will, therefore, be needed to answer the question of whether MPyV binding to the SA residues of a4b1 integrin induces modulation of the integrin activity by promoting exposure of the active binding site for interaction with the VP1 LDV motif.…”

Section: Discussionmentioning

confidence: 99%

Role of sialic acid-containing molecules and the α4β1 integrin receptor in the early steps of polyomavirus infection

Caruso

Cavaldesi

Gentile

et al. 2003

Journal of General Virology

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Murine polyomavirus (MPyV) infection occurs through recognition of sialic acid (SA) residues present on the host cell membrane, but the nature of the molecules involved and the exact role of this interaction in virus cell entry still need to be clarified. In this work, mutations at residues R 77 or H 298 of the MPyV VP1 protein were shown to lead to a complete loss of virus infectivity, which, however, could be restored by lipofection of virus particles into the cytoplasm of the host cells. Using virus-like particles (VLPs), it was demonstrated that the non-infectivity of these mutants was due to impaired cell entry caused by total abrogation of SA-dependent cell binding. This indicates that SA residues are essential primary cell receptors for MPyV. As the a4b1 integrin has been identified recently as a cell receptor for MPyV, the relationship, if any, was investigated between SA-containing and a4b1 integrin receptors. The ability of mutants R 77 Q and H 298 Q and wt VLPs to bind to cells overexpressing the a4b1 integrin was studied in SA-positive (BALB/c 3T3 cells and Pro-5 cells) and SA-deficient (Pro5-derived Lec-2 cells) backgrounds. Overexpression of a4b1 integrin did not restore binding of mutant VLPs in any of these cell lines or, indeed, that of wt VLPs in a SA-deficient background. Moreover, evidence is provided that overexpression of the sialylated a4b1 integrin enhances wt VLP cell binding, suggesting that, in addition to its function at a post-attachment level, a4b1 integrin acts also as one of the SA-containing receptors for initial cell binding.

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Sialidase Treatment Exposes the βT1-Integrin Active Ligand Binding Site on HL60 Cells and Increases Binding to Fibronectin

Cited by 46 publications

References 46 publications

Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth

Hyposialylation of Integrins Stimulates the Activity of Myeloid Fibronectin Receptors

Role of sialic acid-containing molecules and the α4β1 integrin receptor in the early steps of polyomavirus infection

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