scholarly journals Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0249905
Author(s):  
Shivani Ahuja ◽  
James Cahill ◽  
Kimberly Hartfield ◽  
Matthew R. Whorton
Keyword(s):  
Sialic Acid ◽  
Acid Transport ◽  
Gene Expression And Regulation ◽  
Transport Activity ◽  
Nucleotide Sugar ◽  
Control Of Gene Expression ◽  
Sugar Transporters ◽  
Physiological Regulator ◽  
Nucleotide Sugar Transporters ◽  
Epigenetic Processes

Nucleotide-sugar transporters (NSTs) transport nucleotide-sugar conjugates into the Golgi lumen where they are then used in the synthesis of glycans. We previously reported crystal structures of a mammalian NST, the CMP-sialic acid transporter (CST) (Ahuja and Whorton 2019). These structures elucidated many aspects of substrate recognition, selectivity, and transport; however, one fundamental unaddressed question is how the transport activity of NSTs might be physiologically regulated as a means to produce the vast diversity of observed glycan structures. Here, we describe the discovery that an endogenous methylated form of cytidine monophosphate (m5CMP) binds and inhibits CST. The presence of m5CMP in cells results from the degradation of RNA that has had its cytosine bases post-transcriptionally methylated through epigenetic processes. Therefore, this work not only demonstrates that m5CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.

scholarly journals Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP

2020 ◽  
Author(s):  
Shivani Ahuja ◽  
James Cahill ◽  
Kimberly Hartfield ◽  
Matthew R. Whorton
Keyword(s):  
Sialic Acid ◽  
Acid Transport ◽  
Gene Expression And Regulation ◽  
Transport Activity ◽  
Nucleotide Sugar ◽  
Control Of Gene Expression ◽  
Sugar Transporters ◽  
Physiological Regulator ◽  
Nucleotide Sugar Transporters ◽  
Epigenetic Processes

AbstractNucleotide-sugar transporters (NSTs) transport nucleotide-sugar conjugates into the Golgi lumen where they are then used in the synthesis of glycans. We previously reported crystal structures of a mammalian NST, the CMP-sialic acid transporter (CST) (Ahuja and Whorton 2019). These structures elucidated many aspects of substrate recognition, selectivity, and transport; however, one fundamental unaddressed question is how the transport activity of NSTs might be physiologically regulated as a means to produce the vast diversity of observed glycan structures. Here, we describe the discovery that an endogenous methylated form of cytidine monophosphate (m5CMP) binds and inhibits CST. The presence of m5CMP in cells results from the degradation of RNA that has had its cytosine bases post-transcriptionally methylated through epigenetic processes. Therefore, this work not only demonstrates that m5CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.

Characterization of rice nucleotide sugar transporters capable of transporting UDP-galactose and UDP-glucose

2010 ◽  
Vol 148 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Junichi Seino ◽  
Kumiko Ishii ◽  
Takeshi Nakano ◽  
Nobuhiro Ishida ◽  
Masafumi Tsujimoto ◽  
...  
Keyword(s):  
Nucleotide Sugar ◽  
Sugar Transporters ◽  
Nucleotide Sugar Transporters

scholarly journals Nucleotide sugar transporters of Trypanosoma brucei: glycosylation and infectivity

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Li Liu ◽  
Yu-Xin Xu ◽  
Barbara A. Burleigh ◽  
James D. Bangs ◽  
Carlos B. Hirschberg
Keyword(s):  
Trypanosoma Brucei ◽  
Nucleotide Sugar ◽  
Sugar Transporters ◽  
Nucleotide Sugar Transporters

scholarly journals Biosynthesis of GlcNAc-rich N- and O-glycans in the Golgi apparatus does not require the nucleotide sugar transporter SLC35A3

2020 ◽  
Vol 295 (48) ◽  
pp. 16445-16463 ◽  
Author(s):  
Bozena Szulc ◽  
Paulina Sosicka ◽  
Dorota Maszczak-Seneczko ◽  
Edyta Skurska ◽  
Auhen Shauchuk ◽  
...  
Keyword(s):  
Golgi Apparatus ◽  
Hepg2 Cells ◽  
Double Knockout ◽  
Nucleotide Sugar ◽  
Sugar Transporters ◽  
Nucleotide Sugars ◽  
Nucleotide Sugar Transporters ◽  
Hepg2 Cell Lines ◽  
Nucleotide Sugar Transporter ◽  
Qualitative Changes

Nucleotide sugar transporters, encoded by the SLC35 gene family, deliver nucleotide sugars throughout the cell for various glycosyltransferase-catalyzed glycosylation reactions. GlcNAc, in the form of UDP-GlcNAc, and galactose, as UDP-Gal, are delivered into the Golgi apparatus by SLC35A3 and SLC35A2 transporters, respectively. However, although the UDP-Gal transporting activity of SLC35A2 has been clearly demonstrated, UDP-GlcNAc delivery by SLC35A3 is not fully understood. Therefore, we analyzed a panel of CHO, HEK293T, and HepG2 cell lines including WT cells, SLC35A2 knockouts, SLC35A3 knockouts, and double-knockout cells. Cells lacking SLC35A2 displayed significant changes in N- and O-glycan synthesis. However, in SLC35A3-knockout CHO cells, only limited changes were observed; GlcNAc was still incorporated into N-glycans, but complex type N-glycan branching was impaired, although UDP-GlcNAc transport into Golgi vesicles was not decreased. In SLC35A3-knockout HEK293T cells, UDP-GlcNAc transport was significantly decreased but not completely abolished. However, N-glycan branching was not impaired in these cells. In CHO and HEK293T cells, the effect of SLC35A3 deficiency on N-glycan branching was potentiated in the absence of SLC35A2. Moreover, in SLC35A3-knockout HEK293T and HepG2 cells, GlcNAc was still incorporated into O-glycans. However, in the case of HepG2 cells, no qualitative changes in N-glycans between WT and SLC35A3 knockout cells nor between SLC35A2 knockout and double-knockout cells were observed. These findings suggest that SLC35A3 may not be the primary UDP-GlcNAc transporter and/or different mechanisms of UDP-GlcNAc transport into the Golgi apparatus may exist.

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