Beta3Gn-T7 Is a Keratan Sulfate β1,3 N-Acetylglucosaminyltransferase in the Adult Brain

Takeda-Uchimura, Yoshiko; Nishitsuji, Kazuchika; Ikezaki, Midori; Akama, Tomoya O.; Ihara, Yoshito; Allain, Fabrice; Uchimura, Kenji

doi:10.3389/fnana.2022.813841

Cited by 9 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although B3GnT3, 4 and 9 showed some polyLacNAc synthesis activity towards LRP6, albeit lower than B3GnT2, they either had no significant effect (B3GnT4) or an inhibitory effect (B3GnT3 and 9) on LRP/Wnt signalling ( Figure S3c ). Interestingly, B3GnT7, which is reported to synthesise keratin sulphate (KS) by adding N-acetylglucosamine to KS glycosaminoglycans [ 57 , 58 , 59 ], showed the strongest inhibition of LRP6/Wnt signalling of any family member and induced a weakly diffuse but large upshift of the upper LRP6 protein band together with a strong LEL signal ( Figure S3b,c ). Nevertheless, B3GnT7 failed to significantly alter B3GnT2-induced LRP6/Wnt signalling when compared to other members ( Figure S2c ).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to B3GnT2 and 8, other members have been implicated in the synthesis of polyLacNAc chains, such as B3GnT3 [ 63 ], and we have also shown that B3GnT3, 4, 7 and 9 can synthesise polyLacNAc on LRP6. It remains unclear why B3GnT7, which is reported to be specific for sulphated LacNAc chains present in keratin sulphate glycosaminoglycans [ 57 , 59 ], should stain positive for the polyLacNAc selective lectin, LEL. Like B3GnT2, which recognises and elongates LacNAc disaccharides in conjunction with B4GalT family members, B3GnT7 elongates LacNAc disaccharides; however, the N-acetylglucosaminyltransferase activity of B3GnT7 is thought to be specific for GlcNAc-6-sulphated LacNAc-containing glycans [ 59 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

N-Glycosylation of LRP6 by B3GnT2 Promotes Wnt/β-Catenin Signalling

Wang

Safi

et al. 2023

Cells

View full text Add to dashboard Cite

Reception of Wnt signals by cells is predominantly mediated by Frizzled receptors in conjunction with a co-receptor, the latter being LRP6 or LRP5 for the Wnt/β-catenin signalling pathway. It is important that cells maintain precise control of receptor activation events in order to properly regulate Wnt/β-catenin signalling as aberrant signalling can result in disease in humans. Phosphorylation of the intracellular domain (ICD) of LRP6 is well known to regulate Wntβ-catenin signalling; however, less is known for regulatory post-translational modification events within the extracellular domain (ECD). Using a cell culture-based expression screen for functional regulators of LRP6, we identified a glycosyltransferase, B3GnT2-like, from a teleost fish (medaka) cDNA library, that modifies LRP6 and regulates Wnt/β-catenin signalling. We provide both gain-of-function and loss-of-function evidence that the single human homolog, B3GnT2, promotes extension of polylactosamine chains at multiple N-glycans on LRP6, thereby enhancing trafficking of LRP6 to the plasma membrane and promoting Wnt/β-catenin signalling. Our findings further highlight the importance of LRP6 as a regulatory hub in Wnt signalling and provide one of the few examples of how a specific glycosyltransferase appears to selectively target a signalling pathway component to alter cellular signalling events.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

N-Glycosylation of LRP6 by B3GnT2 Promotes Wnt/β-Catenin Signalling

Wang

Safi

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

“…Protein-tyrosine phosphatase receptor type z1 (Ptprz1)/phosphacan in PNNs contain low sulfation KS. Extension of the KS is undertaken with GlcNAc by β1,3 N -acetylglucosaminyltransferase (Beta3Gn-T) ( Takeda-Uchimura et al. 2022 ).…”

Section: Phosphacanmentioning

confidence: 99%

Keratan sulfate, an electrosensory neurosentient bioresponsive cell instructive glycosaminoglycan

Melrose

2024

Glycobiology

View full text Add to dashboard Cite

The roles of keratan sulfate (KS) as a proton detection glycosaminoglycan in neurosensory processes in the central and peripheral nervous systems is reviewed. The functional properties of the KS-proteoglycans aggrecan, phosphacan, podocalyxcin as components of perineuronal nets in neurosensory processes in neuronal plasticity, cognitive learning and memory are also discussed. KS-glycoconjugate neurosensory gels used in electrolocation in elasmobranch fish species and KS substituted mucin like conjugates in some tissue contexts in mammals need to be considered in sensory signalling. Parallels are drawn between KS’s roles in elasmobranch fish neurosensory processes and its roles in mammalian electro mechanical transduction of acoustic liquid displacement signals in the cochlea by the tectorial membrane and stereocilia of sensory inner and outer hair cells into neural signals for sound interpretation. The sophisticated structural and functional proteins which maintain the unique high precision physical properties of stereocilia in the detection, transmittance and interpretation of acoustic signals in the hearing process are important. The maintenance of the material properties of stereocilia are essential in sound transmission processes. Specific, emerging roles for low sulfation KS in sensory bioregulation are contrasted with the properties of high charge density KS isoforms. Some speculations are made on how the molecular and electrical properties of KS may be of potential application in futuristic nanoelectronic, memristor technology in advanced ultrafast computing devices with low energy requirements in nanomachines, nanobots or molecular switches which could be potentially useful in artificial synapse development. Application of KS in such innovative areas in bioregulation are eagerly awaited.

show abstract

“…GlcNAc6ST2 and GlcNAc6ST3 are complementary to the synthesis of CL40-reactive sialylated sulfated glycans in the mouse pleural mesothelium. Since we previously showed that the synthesis of cerebral R-10G-positive KS in which the predicted minimum epitope is an asialo 6-sulfo di-LacNAc [ 4 , 5 , 6 , 7 ] is GlcNAc6ST-dependent and that GlcNAc6ST3 is a major GlcNAc6ST in the adult brain [ 8 , 9 , 10 ], we tested the possibility that R-10G-reactive KS is also present in the pleural mesothelium. The question of which GlcNAc6STs are responsible for the synthesis of R-10G-reactive glycans was elucidated as well.…”

Section: Introductionmentioning

confidence: 99%

GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-Acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

Takeda-Uchimura,

Ikezaki,

Akama

et al. 2024

Molecules

Self Cite

View full text Add to dashboard Cite

We recently showed that 6-sulfo sialyl N-acetyllactosamine (LacNAc) in O-linked glycans recognized by the CL40 antibody is abundant in the pleural mesothelium under physiological conditions and that these glycans undergo complementary synthesis by GlcNAc6ST2 (encoded by Chst4) and GlcNAc6ST3 (encoded by Chst5) in mice. GlcNAc6ST3 is essential for the synthesis of R-10G-positive keratan sulfate (KS) in the brain. The predicted minimum epitope of the R-10G antibody is a dimeric asialo 6-sulfo LacNAc. Whether R-10G-reactive KS/sulfated LacNAc oligosaccharides are also present in the pleural mesothelium was unknown. The question of which GlcNAc6STs are responsible for R-10G-reactive glycans was an additional issue to be clarified. Here, we show that R-10G-reactive glycans are as abundant in the pulmonary pleura as CL40-reactive glycans and that GlcNAc6ST3 is only partially involved in the synthesis of these pleural R-10G glycans, unlike in the adult brain. Unexpectedly, GlcNAc6ST2 is essential for the synthesis of R-10G-positive KS/sulfated LacNAc oligosaccharides in the lung pleura. The type of GlcNAc6ST and the magnitude of its contribution to KS glycan synthesis varied among tissues in vivo. We show that GlcNAc6ST2 is required and sufficient for R-10G-reactive KS synthesis in the lung pleura. Interestingly, R-10G immunoreactivity in KSGal6ST (encoded by Chst1) and C6ST1 (encoded by Chst3) double-deficient mouse lungs was markedly increased. MUC16, a mucin molecule, was shown to be a candidate carrier protein for pleural R-10G-reactive glycans. These results suggest that R-10G-reactive KS/sulfated LacNAc oligosaccharides may play a role in mesothelial cell proliferation and differentiation. Further elucidation of the functions of sulfated glycans synthesized by GlcNAc6ST2 and GlcNAc6ST3, such as R-10G and CL40 glycans, in pathological conditions may lead to a better understanding of the underlying mechanisms of the physiopathology of the lung mesothelium.

show abstract

Beta3Gn-T7 Is a Keratan Sulfate β1,3 N-Acetylglucosaminyltransferase in the Adult Brain

Cited by 9 publications

References 56 publications

N-Glycosylation of LRP6 by B3GnT2 Promotes Wnt/β-Catenin Signalling

N-Glycosylation of LRP6 by B3GnT2 Promotes Wnt/β-Catenin Signalling

Keratan sulfate, an electrosensory neurosentient bioresponsive cell instructive glycosaminoglycan

GlcNAc6ST2/CHST4 Is Essential for the Synthesis of R-10G-Reactive Keratan Sulfate/Sulfated N-Acetyllactosamine Oligosaccharides in Mouse Pleural Mesothelium

Contact Info

Product

Resources

About