Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2

Ward, Jeffrey L.; Leung, George Pak-Heng; Toan, Shuy Vang; Tse, Chung Ming

doi:10.1016/s0003-9861(02)00718-x

Cited by 28 publications

(20 citation statements)

References 20 publications

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“…(6A)) [205]. hENT1 is N-glycosylated at a single site, and hENT2 at two sites, in the large extracellular loops linking TMs 1 and 2, but glycosylation is not required for activity or for plasma membrane targeting of either protein [206,207]. h/mENT3 also have a potential glycosylation site in the TM 1-2 loops [8], and h/mENT4 have a site in the C-terminal tail regions of the proteins [9].…”

Section: Ent Proteinsmentioning

confidence: 99%

Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain

Parkinson¹,

Damaraju²,

Graham³

et al. 2011

CTMC

167

149

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Pyrimidine and purine nucleosides and their derivatives have critical functions and pharmacological applications in the brain. Nucleosides and nucleobases are precursors of nucleotides, which serve as the energy-rich currency of intermediary metabolism and as precursors of nucleic acids. Nucleosides (e.g., adenosine) and nucleotides are key signaling molecules that modulate brain function through interaction with cell surface receptors. Brain pathologies involving nucleosides and their metabolites range from epilepsy to neurodegenerative disorders and psychiatric conditions to cerebrovascular ischemia. Nucleoside analogs are used clinically in the treatment of brain cancer and viral infections. Nucleosides are hydrophilic molecules, and transportability across cell membranes via specialized nucleoside transporter (NT) proteins is a critical determinant of their metabolism and, for nucleoside drugs, their pharmacologic actions. In mammals, there are two types of nucleoside transport process: bidirectional equilibrative processes driven by chemical gradients, and unidirectional concentrative processes driven by sodium (and proton) electrochemical gradients. In mammals, these processes, both of which are present in brain, are mediated by members of two structurally unrelated membrane protein families (ENT and CNT, respectively). In this Chapter, we review current knowledge of cellular, physiological, pathophysiological and therapeutic aspects of ENT and CNT distribution and function in the mammalian brain, including studies with NT inhibitors and new research involving NT knockout and transgenic mice. We also describe recent progress in functional and molecular studies of ENT and CNT proteins, and summarize emerging evidence of other transporter families with demonstrated or potential roles in the transport of nucleosides and their derivatives in the brain.

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Section: Ent Proteinsmentioning

confidence: 99%

Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain

Parkinson¹,

Damaraju²,

Graham³

et al. 2011

CTMC

167

149

View full text Add to dashboard Cite

show abstract

“…2) [40]. hENT1 is N-glycosylated at a single site and hENT2 at two sites in the large extracellular loop linking TM1 and 2, but glycosylation is not essential for activity in either case [44,47]. h/mENT3 similarly bear a glycosylation site in the TM1-2 loop, and h/mENT4 bear a site in the C-terminal tail, but their glycosylation status remains unknown.…”

Section: Structure/function Relationshipsmentioning

confidence: 99%

The equilibrative nucleoside transporter family, SLC29

Baldwin

Beal

Yao

et al. 2004

Pfl�gers Archiv European Journal of Physiology

598

142

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The human SLC29 family of proteins contains four members, designated equilibrative nucleoside transporters (ENTs) because of the properties of the first-characterised family member, hENT1. They belong to the widely-distributed eukaryotic ENT family of equilibrative and concentrative nucleoside/nucleobase transporters and are distantly related to a lysosomal membrane protein, CLN3, mutations in which cause neuronal ceroid lipofuscinosis. A predicted topology of 11 transmembrane helices with a cytoplasmic N-terminus and an extracellular C-terminus has been experimentally confirmed for hENT1. The best-characterised members of the family, hENT1 and hENT2, possess similar broad substrate specificities for purine and pyrimidine nucleosides, but hENT2 in addition efficiently transports nucleobases. The ENT3 and ENT4 isoforms have more recently also been shown to be genuine nucleoside transporters. All four isoforms are widely distributed in mammalian tissues, although their relative abundance varies: ENT2 is particularly abundant in skeletal muscle. In polarised cells ENT1 and ENT2 are found in the basolateral membrane and, in tandem with concentrative transporters of the SLC28 family, may play a role in transepithelial nucleoside transport. The transporters play key roles in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis, and are also responsible for the cellular uptake of nucleoside analogues used in the treatment of cancers and viral diseases. In addition, by regulating the concentration of adenosine available to cell surface receptors, they influence many physiological processes ranging from cardiovascular activity to neurotransmission.

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“…These transporters are post-translationally modified by glycosylation. hENT1 and hENT2 are glycosylated in the extracellular loop lying between TM1 and TM2, hENT1 at Asn48, and hENT2 at Asn48 and Asn57 (Sundaram et al, 2001a;Ward et al, 2003). Glycosylation is not essential for transporter activity, but can modulate the sensitivity to inhibition by NBTI and coronary vasodilators (Vickers et al, 1999).…”

Section: The Slc29 Gene Family: Equilibrative Nucleoside Transportersmentioning

confidence: 99%

Nucleoside Transporters (SLC28 and SLC29) Family

Molina‐Arcas

Pastor‐Anglada

2013

Pharmacogenomics of Human Drug Transporters

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Functional analysis of site-directed glycosylation mutants of the human equilibrative nucleoside transporter-2

Cited by 28 publications

References 20 publications

Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain

Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain

The equilibrative nucleoside transporter family, SLC29

Nucleoside Transporters (SLC28 and SLC29) Family

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