The SLC28 (CNT) and SLC29 (ENT) nucleoside transporter families: a 30-year collaborative odyssey

2016 ◽  
Vol 44 (3) ◽  
pp. 869-876 ◽  
Author(s):  
James D. Young
Keyword(s):  
Cell Signalling ◽  
Cell Types ◽  
Chemotherapeutic Agents ◽  
Nucleoside Analogues ◽  
Nucleoside Transporter ◽  
Protein Families ◽  
Lower Vertebrate ◽  
Nucleotide Biosynthesis ◽  
Cellular Events ◽  
Concentrative Nucleoside Transporter

Specialized nucleoside transporter (NT) proteins are required for passage of nucleosides and hydrophilic nucleoside analogues across biological membranes. Physiologic nucleosides serve as central salvage metabolites in nucleotide biosynthesis, and nucleoside analogues are used as chemotherapeutic agents in the treatment of cancer and antiviral diseases. The nucleoside adenosine modulates numerous cellular events via purino-receptor cell signalling pathways. Human NTs are divided into two structurally unrelated protein families: the SLC28 concentrative nucleoside transporter (CNT) family and the SLC29 equilibrative nucleoside transporter (ENT) family. Human CNTs are inwardly directed Na+-dependent nucleoside transporters found predominantly in intestinal and renal epithelial and other specialized cell types. Human ENTs mediate bidirectional fluxes of purine and pyrimidine nucleosides down their concentration gradients and are ubiquitously found in most, possibly all, cell types. Both protein families are evolutionarily old: CNTs are present in both eukaryotes and prokaryotes; ENTs are widely distributed in mammalian, lower vertebrate and other eukaryote species. This mini-review describes a 30-year collaboration with Professor Stephen Baldwin to identify and understand the structures and functions of these physiologically and clinically important transport proteins.

Recent advances in the molecular biology of nucleoside transporters of mammalian cells

1998 ◽  
Vol 76 (5) ◽  
pp. 761-770 ◽  
Author(s):  
Carol E Cass ◽  
James D Young ◽  
Stephen A Baldwin
Keyword(s):  
Molecular Biology ◽  
Mammalian Cells ◽  
Cell Types ◽  
Functional Expression ◽  
Transport Proteins ◽  
Transport Processes ◽  
Nucleoside Transport ◽  
Nucleoside Transporter ◽  
Protein Families ◽  
Public Data

Nucleosides are hydrophilic molecules and require specialized transport proteins for permeation of cell membranes. There are two types of nucleoside transport processes: equilibrative bidirectional processes driven by chemical gradients and inwardly directed concentrative processes driven by the sodium electrochemical gradient. The equilibrative nucleoside transport processes (es, ei) are found in most mammalian cell types, whereas the concentrative nucleoside transport processes (cit, cif, cib, csg, cs) are present primarily in specialized epithelia. Using a variety of cloning strategies and functional expression in oocytes of Xenopus laevis, we have isolated and characterized cDNAs encoding the rat and human nucleoside transporter proteins of the four major nucleoside transport processes of mammalian cells (es, ei, cit, cif). From the sequence relationships of these proteins with each other and with sequences in the public data bases, we have concluded that the equilibrative and concentrative nucleoside transport processes are mediated by members of two previously unrecognized groups of integral membrane proteins, which we have designated the equilibrative nucleoside transporter (ENT) and the concentrative nucleoside transporter (CNT) protein families. This review summarizes the current state of knowledge in the molecular biology of the ENT and CNT protein families, focusing on the characteristics of the four human (h) and rat (r) nucleoside transport proteins (r/hENT1, r/hENT2, r/hCNT1, r/hCNT2).Key words: nucleoside transporter, equilibrative, concentrative, ENT, CNT.

Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura Campello ◽  
Nivedita Singh ◽  
Jayshree Advani ◽  
Anupam K. Mondal ◽  
Ximena Corso-Diaz ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Cell Types ◽  
Lifestyle Changes ◽  
Annual Review ◽  
Past Century ◽  
Publication Date ◽  
Vision Science ◽  
Human Lifespan ◽  
Cellular Events ◽  
Age Related

Multifaceted and divergent manifestations across tissues and cell types have curtailed advances in deciphering the cellular events that accompany advanced age and contribute to morbidities and mortalities. Increase in human lifespan during the past century has heightened awareness of the need to prevent age-associated frailty of neuronal and sensory systems to allow a healthy and productive life. In this review, we discuss molecular and physiological attributes of aging of the retina, with a goal of understanding age-related impairment of visual function. We highlight the epigenome–metabolism nexus and proteostasis as key contributors to retinal aging and discuss lifestyle changes as potential modulators of retinal function. Finally, we deliberate promising intervention strategies for promoting healthy aging of the retina for improved vision. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Cell-type specific calcium signalling in a Drosophila epithelium

1997 ◽  
Vol 110 (15) ◽  
pp. 1683-1692 ◽  
Author(s):  
P. Rosay ◽  
S.A. Davies ◽  
Y. Yu ◽  
A. Sozen ◽  
K. Kaiser ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Critical Role ◽  
Cell Signalling ◽  
Calcium Signalling ◽  
Malpighian Tubule ◽  
Fluid Secretion ◽  
Cell Types ◽  
Cytosolic Calcium ◽  
Atpase Inhibitor ◽  
Principal Cells

Calcium is a ubiquitous second messenger that plays a critical role in both excitable and non-excitable cells. Calcium mobilisation in identified cell types within an intact renal epithelium, the Drosophila melanogaster Malpighian tubule, was studied by GAL4-directed expression of an aequorin transgene. CAP2b, a cardioactive neuropeptide that stimulates fluid secretion by a mechanism involving nitric oxide, causes a rapid, dose-dependent rise in cytosolic calcium in only a single, genetically-defined, set of 77 principal cells in the main (secretory) segment of the tubule. In the absence of external calcium, the CAP2b-induced calcium response is abolished. In Ca2+-free medium, the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, elevates [Ca2+]i only in the smaller stellate cells, suggesting that principal cells do not contain a thapsigargin-sensitive intracellular pool. Assays for epithelial function confirm that calcium entry is essential for CAP2b to induce a physiological response in the whole organ. Furthermore, the data suggest a role for calcium signalling in the modulation of the nitric oxide signalling pathway in this epithelium. The GAL4-targeting system allows general application to studies of cell-signalling and pharmacology that does not rely on invasive or cytotoxic techniques.

scholarly journals A Comprehensive Modeling Procedure for the Human Granulopoietic System: Over-all View and Summary of Data

Blood ◽  
1973 ◽  
Vol 42 (2) ◽  
pp. 303-313 ◽  
Author(s):  
Leslie E. Blumenson
Keyword(s):  
Peripheral Blood ◽  
Marrow Cell ◽  
Cell Types ◽  
Cellular Level ◽  
Laboratory Research ◽  
Modeling Procedure ◽  
Cellular Events ◽  
Rapid Pace ◽  
The One ◽  
Comprehensive Modeling

Abstract Understanding of the granulopoietic system in both normal and diseased states might be assisted by the use of a quantitative modeling procedure that relates the underlying cellular events of granulopoiesis studied in the laboratory to the marrow and peripheral blood picture as it might be seen in the clinic. In this way, the modeling procedure could become both an adjunct to ongoing laboratory research, as well as a means for rationally deciding on modes of treatment for pathologic conditions. The depth and rapid pace of modern granulopoietic research require that the modeling procedure be, on the one hand, detailed enough to permit the inclusion of the pertinent events at the cellular level as they are known today, while on the other hand, remain flexible enough to permit both the modification of any part and the possibility of seeing the predicted consequences of this modification for both the normal and diseased states. A detailed procedure was developed for an hour-by-hour description of the interrelationship of the kinetics of the various marrow cell types with the events in the peripheral blood and tissue spaces. The model was extended to include the toxic effects of a drug (5-fluorouracil) administered according to the protocol of an actual trial with cancer patients, and the temporal pattern of the predicted effects of the drug on the peripheral blood count was compared with that found in the clinic.

scholarly journals Conserved Glutamate Residues Glu-343 and Glu-519 Provide Mechanistic Insights into Cation/Nucleoside Cotransport by Human Concentrative Nucleoside Transporter hCNT3

2009 ◽  
Vol 284 (25) ◽  
pp. 17266-17280 ◽  
Author(s):  
Melissa D. Slugoski ◽  
Kyla M. Smith ◽  
Amy M. L. Ng ◽  
Sylvia Y. M. Yao ◽  
Edward Karpinski ◽  
...  
Keyword(s):  
Nucleoside Transporter ◽  
Concentrative Nucleoside Transporter

Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function

2015 ◽  
Vol 30 (2) ◽  
pp. 544-554 ◽  
Author(s):  
Paula Fernández‐Calotti ◽  
Olga Casulleras ◽  
María Antolin ◽  
Francisco Guarner ◽  
Marçal Pastor‐Anglada
Keyword(s):  
Nucleoside Transporter ◽  
Drug Transporter ◽  
Concentrative Nucleoside Transporter

A splice variant of the SLC28A3 gene encodes a novel human concentrative nucleoside transporter‐3 (hCNT3) protein localized in the endoplasmic reticulum

2008 ◽  
Vol 23 (1) ◽  
pp. 172-182 ◽  
Author(s):  
Ekaitz Errasti‐Murugarren ◽  
Miriam Molina‐Arcas ◽  
Fco Javier Casado ◽  
Marcal Pastor‐Anglada
Keyword(s):  
Endoplasmic Reticulum ◽  
Splice Variant ◽  
Nucleoside Transporter ◽  
Concentrative Nucleoside Transporter
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