UDP-N-acetylglucosamine Transporter (SLC35A3) Regulates Biosynthesis of Highly Branched N-Glycans and Keratan Sulfate

Maszczak‐Seneczko, Dorota; Sosicka, Paulina; Olczak, Teresa; Jakimowicz, Piotr; Majkowski, Michał; Olczak, Mariusz

doi:10.1074/jbc.m113.460543

Cited by 48 publications

(74 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first finding describes an association between UDP-galactose:ceramide galactosyltransferase and UGT (14). The second report, coming from our laboratory, showed that NGT is in close proximity to Mgat5 (15). However, both findings refer to the experiments performed only on overexpressed proteins.…”

Section: Resultscontrasting

confidence: 38%

“…Recently, it has been discovered that NSTs are also able to form heterologous complexes (13). Moreover, there are two reports on the interactions between NSTs and respective glycosyltransferases (14,15). However, in both cases, the results were derived from overexpression experiments.…”

mentioning

confidence: 53%

“…13 pTag-RFP-C-UGT2 pTag-RFP-C UGT2 Ref. 13 pTag-GFP2-C-Mgat1 pTag-GFP2-C Mgat1 This study pTag-GFP2-C-Mgat2 pTag-GFP2-C Mgat2 This study pTag-GFP2-C-Mgat4B pTag-GFP2-C Mgat4B This study pTag-GFP2-C-Mgat5 pTag-GFP2- For FLIM-FRET experiments, HEK293T cells were grown in DMEM supplemented with 10% fetal bovine serum, 4 mM L-glutamine, 100 units/ml penicillin, and 100 g/ml streptomycin and transiently transfected with expression plasmid(s) as described previously (15). FLIM-FRET analysis was performed 48 h after transfection.…”

Section: Methodsmentioning

confidence: 99%

“…Confocal and FLIM microscopy were performed as described previously (13,15), except that HEK293T cells were used in all experiments, and cells transiently transfected with expression plasmids listed in Table 1 were seeded onto 35-mm CELLview glass bottom dishes (Greiner Bio-One) prior to imaging. Analysis of the data received from FLIM-FRET experiments was carried out as reported previously (13) Statistical Analysis-To analyze whether the differences in mean eGFP fluorescence lifetimes () between control measurements (eGFP-Mgat only) and investigated samples, where the acceptor was present (eGFP-MgatϩmRFP-NST), are statistically significant, one-way analysis of variance was employed.…”

Section: Confocal and Fluorescence Lifetime Imaging Microscopy-mentioning

confidence: 99%

“…Our recent findings strongly suggest that NGT occurs in close proximity to Mgat5 (15) and NGT and UGT form heterologous complexes in the Golgi membrane (13). Based on our previous observations, we aimed to investigate whether these NSTs interact with mannoside acetylglucosaminyltransferases mediating N-glycan biosynthesis, i.e.…”

mentioning

confidence: 99%

See 4 more Smart Citations

UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats)

Maszczak‐Seneczko

Sosicka

Kaczmarek

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: UDP-galactose (UGT) and UDP-N-acetylglucosamine (NGT) transporters and mannoside acetylglucosaminyltransferases (Mgats) are important mediators of N-linked protein glycosylation. Results: UGT and NGT are in close proximity to Mgats. Conclusion: UGT, NGT and Mgats may form multiprotein complexes mediating biosynthesis of N-glycans.Significance: Protein-protein interactions between Golgi-resident nucleotide sugar transporters and glycosyltransferases appears to be an inherent feature of N-linked glycosylation.

show abstract

Section: Resultscontrasting

confidence: 38%

mentioning

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Section: Confocal and Fluorescence Lifetime Imaging Microscopy-mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats)

Maszczak‐Seneczko

Sosicka

Kaczmarek

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

The glycosylation defect in solute carrier SLC35A2/SLC35A3 double knockout cells is rescued by SLC35A2–SLC35A3 and SLC35A3–SLC35A2 hybrids

Wiertelak,

Pavlovskyi,

Maszczak‐Seneczko

et al. 2023

FEBS Letters

Self Cite

View full text Add to dashboard Cite

Abstract:SLC35A2 and SLC35A3 are homologous proteins with postulated nucleotide sugar transporting activities. Unlike SLC35A2, whose specificity for UDP‐Gal is well established, the UDP‐GlcNAc transporting activity initially attributed to SLC35A3 has recently been put into question. In this study, we constructed two hybrid proteins (SLC35A2–SLC35A3 and SLC35A3–SLC35A2) and expressed them in a previously generated SLC35A2/SLC35A3 double knockout HEK293T cell line. Our idea was to force equivalent stoichiometry of the two proteins in the cells in order to reproduce the behavior of the SLC35A2/SLC35A3 complexes in the Golgi membrane. The hybrid proteins were able to fully restore glycosylation in the double knockout. In contrast, the expression of SLC35A3 alone in these cells improved galactosylation only to a limited extent. Our study shows that the proper glycosylation requires a balanced cooperation between SLC35A2 and SLC35A3.

show abstract

A human case of SLC35A3‐related skeletal dysplasia

Edmondson

Bedoukian

Deardorff

et al. 2017

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Researchers have identified a subset of Holstein having a range of skeletal deformities, including vertebral anomalies, referred to as complex vertebral malformation due to mutations in the SLC35A3 gene. Here, we report the first case in humans of SLC35A3-related vertebral anomalies. Our patient had prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Clinical exome sequencing revealed a novel missense homozygous mutation in SLC35A3. Follow-up biochemical analysis confirmed abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter, validating the mutations. Congenital disorders of glycosylation, including SLC35A3-CDG, can present as a wide phenotypic spectrum, including skeletal dysplasia. Previously reported patients with SLC35A3-CDG have been described with syndromic autism, epilepsy, and arthrogryposis.

show abstract

UDP-N-acetylglucosamine Transporter (SLC35A3) Regulates Biosynthesis of Highly Branched N-Glycans and Keratan Sulfate

Cited by 48 publications

References 38 publications

UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats)

UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases (Mgats)

The glycosylation defect in solute carrier SLC35A2/SLC35A3 double knockout cells is rescued by SLC35A2–SLC35A3 and SLC35A3–SLC35A2 hybrids

A human case of SLC35A3‐related skeletal dysplasia

Contact Info

Product

Resources

About