Structure-Function Analysis of the Human Sialyltransferase ST3Gal I

Jeanneau, Charlotte; Chazalet, V.; Augé, Claudine; Soumpasis, Dikeos Mario; Harduin-Lepers, Anne; Delannoy, Philippe; Imberty, Anne; Breton, C.

doi:10.1074/jbc.m311764200

Cited by 105 publications

(51 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Tshz2 gene has not been reported to be related to AD; however Tshz3, which is an isomer of Tshz2, is known to have reduced expression in AD [39]. It has also been reported that St3gal1 has four N-glycan attachment sites in its catalytic domain that are potentially glycosylated [40]. Moreover, BACE1 is known to have several N-linked glycosylation sites and N-glycosylation is important for enzymatic activity of BACE1 [28].…”

Section: Discussionmentioning

confidence: 99%

1950 MHz Electromagnetic Fields Ameliorate Aβ Pathology in Alzheimer’s Disease Mice

Jeong¹,

Kang²,

Kwon³

et al. 2015

CAR

View full text Add to dashboard Cite

The involvement of radiofrequency electromagnetic fields (RF-EMF) in the neurodegenerative disease, especially Alzheimer’s disease (AD), has received wide consideration, however, outcomes from several researches have not shown consistency. In this study, we determined whether RF-EMF influenced AD pathology in vivo using Tg-5xFAD mice as a model of AD-like amyloid β (Aβ) pathology. The transgenic (Tg)-5xFAD and wild type (WT) mice were chronically exposed to RF-EMF for 8 months (1950 MHz, SAR 5W/kg, 2 hrs/day, 5 days/week). Notably, chronic RF-EMF exposure significantly reduced not only Aβ plaques, APP, and APP carboxyl-terminal fragments (CTFs) in whole brain including hippocampus and entorhinal cortex but also the ratio of Aβ42 and Aβ40 peptide in the hippocampus of Tg-5xFAD mice. We also found that parenchymal expression of β-amyloid precursor protein cleaving enzyme 1(BACE1) and neuroinflammation were inhibited by RF-EMF exposure in Tg-5xFAD. In addition, RF-EMF was shown to rescue memory impairment in Tg-5xFAD. Moreover, gene profiling from microarray data using hippocampus of WT and Tg-5xFAD following RF-EMF exposure revealed that 5 genes (Tshz2, Gm12695, St3gal1, Isx and Tll1), which are involved in Aβ, are significantly altered inTg-5xFAD mice, exhibiting different responses to RF-EMF in WT or Tg-5xFAD mice; RF-EMF exposure in WT mice showed similar patterns to control Tg-5xFAD mice, however, RF-EMF exposure in Tg-5xFAD mice showed opposite expression patterns. These findings indicate that chronic RF-EMF exposure directly affects Aβ pathology in AD but not in normal brain. Therefore, RF-EMF has preventive effects against AD-like pathology in advanced AD mice with a high expression of Aβ, which suggests that RF-EMF can have a beneficial influence on AD.

show abstract

Section: Discussionmentioning

confidence: 99%

1950 MHz Electromagnetic Fields Ameliorate Aβ Pathology in Alzheimer’s Disease Mice

Jeong¹,

Kang²,

Kwon³

et al. 2015

CAR

View full text Add to dashboard Cite

show abstract

“…An additional 4-amino acid motif, motif III, is conserved in the sialyltransferases (42)(43)(44). It was suggested that this motif, and particularly His and Tyr residues within its sequence, may be required for optimal activity and acceptor recognition (42). Angata et al (45) used chimeric enzymes to identify regions within the polySTs required for catalytic activity and NCAM polysialylation.…”

mentioning

confidence: 99%

Identification of Sequences in the Polysialyltransferases ST8Sia II and ST8Sia IV That Are Required for the Protein-specific Polysialylation of the Neural Cell Adhesion Molecule, NCAM

Foley¹,

Swartzentruber²,

Colley

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The polysialyltransferases ST8Sia II and ST8Sia IV polysialylate the glycans of a small subset of mammalian proteins. Their most abundant substrate is the neural cell adhesion molecule (NCAM). An acidic surface patch and a novel ␣-helix in the first fibronectin type III repeat of NCAM are required for the polysialylation of N-glycans on the adjacent immunoglobulin domain. Inspection of ST8Sia IV sequences revealed two conserved polybasic regions that might interact with the NCAM acidic patch or the growing polysialic acid chain. One is the previously identified polysialyltransferase domain (Nakata, D., Zhang, L., and Troy, F. A. (2006) Glycoconj. J. 23, 423-436). The second is a 35-amino acid polybasic region that contains seven basic residues and is equidistant from the large sialyl motif in both polysialyltransferases. We replaced these basic residues to evaluate their role in enzyme autopolysialylation and NCAM-specific polysialylation. We found that replacement of Arg . Replacement of these residues with alanine largely inactivated ST8Sia IV, whereas reversing these residues enhanced enzyme autopolysialylation but significantly reduced NCAM polysialylation. In sum, we have identified selected amino acids in this conserved polysialyltransferase polybasic region that are critical for the protein-specific polysialylation of NCAM.Polysialic acid is a linear homopolymer of ␣2,8-linked sialic acid that is added to a small subset of mammalian glycoproteins by the polysialyltransferases (polySTs) 3 ST8Sia II (STX) and ST8Sia IV (PST) (1-4). Substrates for the polySTs include the neural cell adhesion molecule (NCAM) (5, 6), the ␣-subunit of the voltage-dependent sodium channel (7, 8), CD36, a scavenger receptor found in milk (9), neuropilin-2 expressed by dendritic cells (10), and the polySTs themselves, which can polysialylate their own N-glycans in a process called autopolysialylation (11,12). This small number of polysialylated proteins and other evidence from our laboratory (13-15) suggest that polysialylation is a protein-specific modification that requires an initial protein-protein interaction between the polySTs and their glycoprotein substrates. The most abundant polysialylated protein is NCAM. The three major NCAM isoforms consist of five Ig domains, two fibronectin type III repeats, and a transmembrane domain and cytoplasmic tail (NCAM140 and NCAM180) or a glycosylphosphatidylinositol anchor (NCAM120) (16). Polysialylation takes place primarily on two N-linked glycans in the Ig5 domain (17). We have previously shown that a truncated NCAM140 protein consisting of Ig5, the first fibronectin type III repeat (FN1), the transmembrane region, and cytoplasmic tail is fully polysialylated (13). However, a protein consisting of Ig5, the transmembrane region, and cytoplasmic tail is not polysialylated (13). This suggests that the polySTs recognize and bind the FN1 domain to polysialylate N-glycans on the adjacent Ig5 domain. We subsequently identified an acidic patch unique to NCAM FN1, consisting of Asp 497 , Asp 5...

show abstract

“…The catalytic domain of animal sialyltransferases contains highly conserved motifs called sialyl motifs L (Long), S (Short), III, and VS (Very Short). [4][5][6][7] Sialyl motif L is characterized by a 45-60 amino acid region in the center of the protein, and it has been found to be involved in the binding of a donor substrate, CMP-Sia. 8) Sialyl motif S is located in the C-terminal region and consists of a 20-30 amino acid stretch.…”

Section: Structure Of Sialyltransferasesmentioning

confidence: 99%

“…6,10) Recently, the existence of a new motif (motif III), which is located between sialyl motifs S and VS and has the consensus sequence of (H/y)Y(Y/F/W/h)(E/D/q/g), has been reported. 6) This motif is also involved in catalytic activity. Sialyltransferases from a myxoma virus, insects, and other invertebrates also have these structural features.…”

Section: )mentioning

confidence: 99%

Characterization of Mouse Sialyltransferase Genes: Their Evolution and Diversity

Takashima¹

2008

Bioscience, Biotechnology, and Biochemistry

110

View full text Add to dashboard Cite

Structure-Function Analysis of the Human Sialyltransferase ST3Gal I

Cited by 105 publications

References 31 publications

1950 MHz Electromagnetic Fields Ameliorate Aβ Pathology in Alzheimer’s Disease Mice

1950 MHz Electromagnetic Fields Ameliorate Aβ Pathology in Alzheimer’s Disease Mice

Identification of Sequences in the Polysialyltransferases ST8Sia II and ST8Sia IV That Are Required for the Protein-specific Polysialylation of the Neural Cell Adhesion Molecule, NCAM

Characterization of Mouse Sialyltransferase Genes: Their Evolution and Diversity

Contact Info

Product

Resources

About