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Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling

(2010) CELLULAR SIGNALLING. 22(2). p.314-324
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Abstract
The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2, -3 and -4 forms a complex with TLR-2, -3 and -4 receptors on the cell-surfacemembrane of naïve and activated macrophage cells (Glycoconj J DOI 10.1007/ s10719-009-9239-8). Activation of Neu1 is induced by TLR ligands binding to their respective receptors. Here,we show that endotoxin lipopolysaccharide (LPS)-induced MyD88/TLR4 complex formation and subsequent NFκB activation is dependent on the removal ofα-2,3-sialyl residue linked to β-galactoside of TLR4 by theNeu1 activity associated with LPS-stimulated live primary macrophage cells,macrophage and dendritic cell lines but not with primary Neu1-deficient macrophage cells. Exogenous α-2,3 sialyl specific neuraminidase (Streptoccocus pneumoniae) and wild-type T. cruzi trans-sialidase (TS) but not the catalytically inactive mutant TSΔAsp98-Glu mediate TLR4 dimerization to facilitate MyD88/TLR4 complex formation and NFκB activation similar to those responses seen with LPS. These same TLR ligand-induced NFκB responses are not observed in TLR deficient HEK293 cells, but are re-established in HEK293 cells stably transfected with TLR4/MD2, and are significantly inhibited by α-2,3-sialyl specific Maackia amurensis (MAL-2) lectin, α-2,3-sialyl specific galectin-1 and neuraminidase inhibitor Tamiflu but not by α-2,6-sialyl specific Sambucus nigra lectin (SNA). Taken together, the findings suggest that Neu1 desialylation of α-2,3-sialyl residues of TLR receptors enables in removing a steric hinderance to receptor association for TLR activation and cellular signaling.
Keywords
NF-KAPPA-B, TRYPANOSOMA-CRUZI, VASCULAR ENDOTHELIAL-CELLS, TRANS-SIALIDASE, FUNCTIONAL DIVERSITY, GLYCAN INTERACTIONS, SURFACE EXPRESSION, EXOGENOUS ANTIGENS, IMMUNE-RESPONSES, CLASS-I

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MLA
Amith, SR et al. “Neu1 Desialylation of Sialyl Alpha-2,3-linked Beta-galactosyl Residues of TOLL-like Receptor 4 Is Essential for Receptor Activation and Cellular Signaling.” CELLULAR SIGNALLING 22.2 (2010): 314–324. Print.
APA
Amith, S., Jayanth, P., Franchuk, S., Finlay, T., Seyrantepe, V., Beyaert, R., Pshezhetsky, A., et al. (2010). Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. CELLULAR SIGNALLING, 22(2), 314–324.
Chicago author-date
Amith, SR, P Jayanth, S Franchuk, T Finlay, V Seyrantepe, Rudi Beyaert, AV Pshezhetsky, and MR Szewczuk. 2010. “Neu1 Desialylation of Sialyl Alpha-2,3-linked Beta-galactosyl Residues of TOLL-like Receptor 4 Is Essential for Receptor Activation and Cellular Signaling.” Cellular Signalling 22 (2): 314–324.
Chicago author-date (all authors)
Amith, SR, P Jayanth, S Franchuk, T Finlay, V Seyrantepe, Rudi Beyaert, AV Pshezhetsky, and MR Szewczuk. 2010. “Neu1 Desialylation of Sialyl Alpha-2,3-linked Beta-galactosyl Residues of TOLL-like Receptor 4 Is Essential for Receptor Activation and Cellular Signaling.” Cellular Signalling 22 (2): 314–324.
Vancouver
1.
Amith S, Jayanth P, Franchuk S, Finlay T, Seyrantepe V, Beyaert R, et al. Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. CELLULAR SIGNALLING. NEW YORK: ELSEVIER SCIENCE INC; 2010;22(2):314–24.
IEEE
[1]
S. Amith et al., “Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling,” CELLULAR SIGNALLING, vol. 22, no. 2, pp. 314–324, 2010.
@article{861806,
  abstract     = {The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2, -3 and -4 forms a complex with TLR-2, -3 and -4 receptors on the cell-surfacemembrane of naïve and activated macrophage cells (Glycoconj J DOI 10.1007/ s10719-009-9239-8). Activation of Neu1 is induced by TLR ligands binding to their respective receptors. Here,we show that endotoxin lipopolysaccharide (LPS)-induced MyD88/TLR4 complex formation and subsequent NFκB
activation is dependent on the removal ofα-2,3-sialyl residue linked to β-galactoside of TLR4 by theNeu1 activity associated with LPS-stimulated live primary macrophage cells,macrophage and dendritic cell lines but not with primary Neu1-deficient macrophage cells. Exogenous α-2,3 sialyl specific neuraminidase (Streptoccocus pneumoniae) and wild-type T. cruzi trans-sialidase (TS) but not the catalytically inactive mutant TSΔAsp98-Glu mediate TLR4 dimerization to facilitate MyD88/TLR4 complex formation and NFκB activation similar to those responses seen with LPS. These same TLR ligand-induced NFκB responses are not observed in TLR deficient HEK293 cells, but are re-established in HEK293 cells stably transfected with TLR4/MD2, and are significantly inhibited by α-2,3-sialyl specific Maackia amurensis (MAL-2) lectin, α-2,3-sialyl specific galectin-1 and neuraminidase inhibitor Tamiflu but not by α-2,6-sialyl specific Sambucus nigra lectin (SNA). Taken together, the findings suggest that Neu1 desialylation of α-2,3-sialyl residues of TLR receptors enables in removing a steric hinderance to receptor association for TLR activation and cellular signaling.},
  author       = {Amith, SR and Jayanth, P and Franchuk, S and Finlay, T and Seyrantepe, V and Beyaert, Rudi and Pshezhetsky, AV and Szewczuk, MR},
  issn         = {0898-6568},
  journal      = {CELLULAR SIGNALLING},
  keywords     = {NF-KAPPA-B,TRYPANOSOMA-CRUZI,VASCULAR ENDOTHELIAL-CELLS,TRANS-SIALIDASE,FUNCTIONAL DIVERSITY,GLYCAN INTERACTIONS,SURFACE EXPRESSION,EXOGENOUS ANTIGENS,IMMUNE-RESPONSES,CLASS-I},
  language     = {eng},
  number       = {2},
  pages        = {314--324},
  publisher    = {ELSEVIER SCIENCE INC},
  title        = {Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling},
  url          = {http://dx.doi.org/10.1016/j.cellsig.2009.09.038},
  volume       = {22},
  year         = {2010},
}

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