SLC35A5 Protein-A Golgi Complex Member with Putative Nucleotide Sugar Transport Activity

Int J Mol Sci. 2019 Jan 11;20(2):276. doi: 10.3390/ijms20020276.

Abstract

Solute carrier family 35 member A5 (SLC35A5) is a member of the SLC35A protein subfamily comprising nucleotide sugar transporters. However, the function of SLC35A5 is yet to be experimentally determined. In this study, we inactivated the SLC35A5 gene in the HepG2 cell line to study a potential role of this protein in glycosylation. Introduced modification affected neither N- nor O-glycans. There was also no influence of the gene knock-out on glycolipid synthesis. However, inactivation of the SLC35A5 gene caused a slight increase in the level of chondroitin sulfate proteoglycans. Moreover, inactivation of the SLC35A5 gene resulted in the decrease of the uridine diphosphate (UDP)-glucuronic acid, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine Golgi uptake, with no influence on the UDP-galactose transport activity. Further studies demonstrated that SLC35A5 localized exclusively to the Golgi apparatus. Careful insight into the protein sequence revealed that the C-terminus of this protein is extremely acidic and contains distinctive motifs, namely DXEE, DXD, and DXXD. Our studies show that the C-terminus is directed toward the cytosol. We also demonstrated that SLC35A5 formed homomers, as well as heteromers with other members of the SLC35A protein subfamily. In conclusion, the SLC35A5 protein might be a Golgi-resident multiprotein complex member engaged in nucleotide sugar transport.

Keywords: Golgi apparatus; glycosylation; nucleotide sugar transporters.

MeSH terms

  • Amino Acid Motifs
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Cytosol / metabolism
  • Gene Knockout Techniques
  • Glycosylation
  • Golgi Apparatus / metabolism*
  • Hep G2 Cells
  • Humans
  • Nucleotide Transport Proteins / chemistry
  • Nucleotide Transport Proteins / genetics*
  • Nucleotide Transport Proteins / metabolism*
  • Solute Carrier Proteins / genetics*
  • Solute Carrier Proteins / metabolism*
  • Uridine Diphosphate Glucuronic Acid / metabolism
  • Uridine Diphosphate N-Acetylglucosamine / metabolism
  • Uridine Diphosphate Sugars / metabolism*

Substances

  • Chondroitin Sulfate Proteoglycans
  • Nucleotide Transport Proteins
  • SLC35A5 protein, human
  • Solute Carrier Proteins
  • Uridine Diphosphate Sugars
  • uridine diphosphate N-acetyllactosamine
  • Uridine Diphosphate Glucuronic Acid
  • Uridine Diphosphate N-Acetylglucosamine