Human dendritic cells contain cell surface sialyltransferase activity

Cabral, M. Guadalupe; Piteira, Ana Rita; Silva, Zélia; Ligeiro, Dário; Brossmer, Reinhard; Videira, Paula A.

doi:10.1016/j.imlet.2010.02.009

Cited by 22 publications

(26 citation statements)

References 33 publications

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“…Although some of the fluorescence in the presence of CMP-5-FITC-NEU could be attributed to uptake and use of CMP-5-FITC-NEU by intracellular sialyltransferases, the strong effect of the ST inhibitor and pretreatment with bacterial neuraminidase argues that RAW cells display genuine ST activity on the cell surface. This result is consistent with previous studies that attributed CMP-5-FITC-NEU fluorescence to ST activity on the cell surface (48,49).…”

Section: Peritoneal Cellssupporting

confidence: 93%

“…Lymph nodes To confirm that the acidic shift in distribution of PrP Sc glycoforms was due to ST activity, two general ST inhibitors, CTP and peracetylated 3F ax -Neu5Ac (FPN), were used (44)(45)(46)(47)(48)(49). In the absence of inhibitors, the distribution of PrP Sc charge glycoforms showed statistically significant shift toward acidic pH after incubation with RAW cells or primary splenocytes for 24 h as before (Fig.…”

Section: Peritoneal Cellsmentioning

confidence: 64%

“…RAW cells showed significant ST activity on their surfaces. ST activity has also been found on the surface of dendritic cells and lymphocytes (48,49). Considering that a number of cells of immune system-including B lymphocytes, monocytes, plasmacytoid dendritic cells, natural killer cells, and others-sequester and disseminate PrP Sc (43,72,78), it is likely that sialylation of PrP Sc is not limited to macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…STs were traditionally thought to localize exclusively in Golgi (50). However, in a growing number of studies, ST activities were found on the surface of a wide variety of immune system cells (48,49,(51)(52)(53). To test whether RAW cells exhibit surface ST activity, we used a fluorescently labeled precursor of sialic acid, CMP-5-FITCneuraminic acid (CMP-5-FITC-NEU), which is a membraneexcluded and sialidase-resistant substrate (54).…”

Section: Peritoneal Cellsmentioning

confidence: 99%

“…Traditionally, STs were thought to localize exclusively within the intracellular secretory apparatus (50). A growing number of studies report ST activity in serum or on surfaces of the cells of immune system, including polymorphonuclear leukocyte, monocyte-derived dendritic cells, lymphocytes, and T cells (48,49,(51)(52)(53)80). Presence of ST on the cell surface or in serum allows rapid restoration or remodeling of the sialylation status of cells without de novo synthesis of cell surface glycoconjugates (48,49,81).…”

Section: Although Degradation Of Prpmentioning

confidence: 99%

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Post-conversion sialylation of prions in lymphoid tissues

Srivastava

Makarava

Katorcha

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Sialylated glycans on the surface of mammalian cells act as part of a "self-associated molecular pattern," helping the immune system to recognize "self" from "altered self" or "nonself." To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrP Sc ) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrP Sc is more sialylated than brain-derived PrP Sc . Enhanced sialylation of PrPSc is recapitulated in vitro by incubating brain-derived PrP Sc with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrP Sc . A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications.prions | prion diseases | sialic acid | sialylated glycans | macrophages

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Section: Peritoneal Cellssupporting

confidence: 93%

Section: Peritoneal Cellsmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Peritoneal Cellsmentioning

confidence: 99%

Section: Although Degradation Of Prpmentioning

confidence: 99%

See 3 more Smart Citations

Post-conversion sialylation of prions in lymphoid tissues

Srivastava

Makarava

Katorcha

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Targeted O‐glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced‐stage bladder tumours

et al. 2017

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Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short‐chain O‐glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl‐Tn(STn) and sialyl‐T(ST), which are generally associated with poor prognosis. We have also explored the nature of T antigen sialylation, namely the sialyl‐3‐T(S3T) and sialyl‐6‐T(S6T) sialoforms, based on combinations of enzymatic treatments. We observed a predominance of sialoglycans over neutral glycoforms (Tn and T antigens) in bladder tumours. In particular, the STn antigen was associated with high‐grade disease and muscle invasion, in accordance with our previous observations. The S3T and S6T antigens were detected for the first time in bladder tumours, but not in healthy urothelia, highlighting their cancer‐specific nature. These glycans were also overexpressed in advanced lesions, especially in cases showing muscle invasion. Glycoproteomic analyses of advanced bladder tumours based on enzymatic treatments, Vicia villosa lectin‐affinity chromatography enrichment and nanoLC‐ESI‐MS/MS analysis resulted in the identification of several key cancer‐associated glycoproteins (MUC16, CD44, integrins) carrying altered glycosylation. Of particular interest were MUC16 STn+‐glycoforms, characteristic of ovarian cancers, which were found in a subset of advanced‐stage bladder tumours facing the worst prognosis. In summary, significant alterations in the O‐glycome and O‐glycoproteome of bladder tumours hold promise for the development of novel noninvasive diagnostic tools and targeted therapeutics. Furthermore, abnormal MUC16 glycoforms hold potential as surrogate biomarkers of poor prognosis and unique molecular signatures for designing highly specific targeted therapeutics.

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Modulation of Voltage‐Gated Ion Channels by Sialylation

Ednie

Bennett

2012

Comprehensive Physiology

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Control and modulation of electrical signaling is vital to normal physiology, particularly in neurons, cardiac myocytes, and skeletal muscle. The orchestrated activities of variable sets of ion channels and transporters, including voltage‐gated ion channels (VGICs), are responsible for initiation, conduction, and termination of the action potential (AP) in excitable cells. Slight changes in VGIC activity can lead to severe pathologies including arrhythmias, epilepsies, and paralyses, while normal excitability depends on the precise tuning of the AP waveform. VGICs are heavily posttranslationally modified, with upward of 30% of the mature channel mass consisting of N‐ and O‐glycans. These glycans are terminated typically by negatively charged sialic acid residues that modulate voltage‐dependent channel gating directly. The data indicate that sialic acids alter VGIC activity in isoform‐specific manners, dependent in part, on the number/location of channel sialic acids attached to the pore‐forming alpha and/or auxiliary subunits that often act through saturating electrostatic mechanisms. Additionally, cell‐specific regulation of sialylation can affect VGIC gating distinctly. Thus, channel sialylation is likely regulated through two mechanisms that together contribute to a dynamic spectrum of possible gating motifs: a subunit‐specific mechanism and regulated (aberrant) changes in the ability of the cell to glycosylate. Recent studies showed that neuronal and cardiac excitability is modulated through regulated changes in voltage‐gated Na + channel sialylation, suggesting that both mechanisms of differential VGIC sialylation contribute to electrical signaling in the brain and heart. Together, the data provide insight into an important and novel paradigm involved in the control and modulation of electrical signaling. © 2012 American Physiological Society. Compr Physiol 2:1269‐1301, 2012.

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Human dendritic cells contain cell surface sialyltransferase activity

Cited by 22 publications

References 33 publications

Post-conversion sialylation of prions in lymphoid tissues

Post-conversion sialylation of prions in lymphoid tissues

Targeted O‐glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced‐stage bladder tumours

Modulation of Voltage‐Gated Ion Channels by Sialylation

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