Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters: evolution and tissue expression

Sreedharan, Smitha; Shaik, Jafar H. A.; Olszewski, Pawel K.; Levine, Allen S.; Schiöth, Helgi B.; Fredriksson, Robert

doi:10.1186/1471-2164-11-17

Cited by 57 publications

(45 citation statements)

References 52 publications

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“…Relatively high levels of VNUT mRNA and/or VNUT immunoreactivity are present in the stomach, intestine, liver, lung, skeletal muscle, thyroid, spleen, blood cells, chemosensory epithelial cells, and keratinocytes [35,[37][38][39][40], suggesting that VNUT-mediated nucleotide entry into the secretory pathway is not restricted to the brain and neuroendocrine tissues. Indeed, VNUT has emerged as a widely expressed nucleotide transporter responsible for the uptake of ATP into secretory granules and vesicles, consequently, contributing to the release of ATP (and likely other nucleotides) from the secretory pathway in a variety of physiologically relevant conditions.…”

Section: Cellular Release Of Nucleotides From the Secretory Pathwaymentioning

confidence: 99%

“…Knocking down SLC17A9 by small interfering RNA (siRNA) decreased KCl-triggered ATP release in PC12 cells [37]. In situ hybridization studies indicated that SLC17A9 transcripts are widely expressed in the brain, with particularly high levels of expression in regions of the hippocampus known to display purinergic neurotransmission [35].…”

Section: Cellular Release Of Nucleotides From the Secretory Pathwaymentioning

confidence: 99%

“…Solute carrier (SLC) 17A9, a member of the SLC17 family of ion transporters [34][35][36], was recently de-orphaned and characterized as a vesicular nucleotide transporter (thereafter named VNUT) that contributes to the release of ATP from a variety of tissues. SLC17A9 is predicted to encode a 430 residue-long protein -dependent ATP transport activity that was inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonate (DIDS) [37].…”

Section: Cellular Release Of Nucleotides From the Secretory Pathwaymentioning

confidence: 99%

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Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

252

225

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Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide-sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.

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Section: Cellular Release Of Nucleotides From the Secretory Pathwaymentioning

confidence: 99%

Section: Cellular Release Of Nucleotides From the Secretory Pathwaymentioning

confidence: 99%

Section: Cellular Release Of Nucleotides From the Secretory Pathwaymentioning

confidence: 99%

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Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

252

225

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“…Since VNUT was reported to be expressed in various tissues, including the lung (25), we hypothesized that VNUT mediates nucleotide uptake in airway epithelial cell mucin granules, thereby contributing to the release of nucleotides from mucinsecreting goblet cells. In this study, we used Calu-3 cells as a model of airway epithelial goblet cells (8,9) to investigate the expression of VNUT in mucin granules and further examined VNUT's contribution to mucin granule nucleotide content and release.…”

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confidence: 99%

Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules

Sesma

Kreda

Okada

et al. 2013

American Journal of Physiology-Cell Physiology

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nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules. Am J Physiol Cell Physiol 304: C976 -C984, 2013. First published March 6, 2013; doi:10.1152/ajpcell.00371.2012.-Nucleotides within the airway surface liquid promote fluid secretion via activation of airway epithelial purinergic receptors. ATP is stored within and released from mucin granules as co-cargo with mucins, but the mechanism by which ATP, and potentially other nucleotides, enter the lumen of mucin granules is not known. We assessed the contribution of the recently identified SLC17A9 vesicle nucleotide transporter (VNUT) to the nucleotide availability within isolated mucin granules and further examined the involvement of VNUT in mucin granule secretion-associated nucleotide release. RT-PCR and Western blot analyses indicated that VNUT is abundantly expressed in airway epithelial goblet-like Calu-3 cells, migrating as a duplex with apparent mobility of 55 and 60 kDa. Subcellular fractionation studies indicated that VNUT55 was associated with high-density mucin granules, whereas VNUT60 was associated with low-density organelles. Immunofluorescence studies showed that recombinant VNUT localized to mucin granules and other organelles. Mucin granules isolated from VNUT short hairpin RNA-expressing cells exhibited a marked reduction of ATP, ADP, AMP, and UTP levels within granules. Ca 2ϩ -regulated vesicular ATP release was markedly reduced in these cells, but mucin secretion was not affected. These results suggest that VNUT is the relevant nucleotide transporter responsible for the uptake of cytosolic nucleotides into mucin granules. By controlling the entry of nucleotides into mucin granules, VNUT contributes to the release of purinergic signaling molecules necessary for the proper hydration of co-released mucins.VNUT; SLC17A9; mucin granules; ATP release; mucin secretion EXTRACELLULAR NUCLEOTIDES are key components of the mucociliary clearance process that traps and removes inhaled particles and microorganisms from the lung. Nucleotides/nucleosides within the airway surface liquid (ASL) promote mucin secretion via activation of P2Y 2 receptors in mucous (goblet) cells and stimulate fluid secretion/mucin hydration via A 2B and P2Y 2 receptor activation in ciliated cells (11). Deficient fluid secretion results in abnormal mucous hydration/clearance, leading to lung failure in cystic fibrosis, the most prevalent potentially lethal genetic disease in the United States and a major factor contributing to the progressive airway obstruction associated with chronic obstructive lung disease (4).Despite the importance of ASL nucleotides in airway physiology, the mechanisms by which airway epithelial cells release nucleotides have just begun to be addressed. For example, we recently demonstrated that plasma membrane pannexin 1 largely contributes to conductive ATP release from normal airways dominated by ciliated cells (22). Deletion of the pannexin 1 gene resulted in impaired ATP release in mouse tracheas ex vivo (22).We also ...

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“…Active plasmalemmal transport of ATP is associated with ABC transporters that are expressed already in protists [221]. Finally, exocytotic ATP release that uses vesicles bearing specific nucleotide transports (VNUT/SLC17A9) allows spatially restricted and tightly regulated ATP release characteristic for nervous system, the VNUT-bearing vesicles are found in invertebrates and characterized in the nematode C. elegans, in sea anemone, in sea urchin and in some insects [222,223]; they are present in vertebrates, where they are expressed in various tissues including the brain [215].…”

Section: Ca 2þ As a Regulator Of Programmed Cell Deathmentioning

confidence: 99%

Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling

Plattner

Verkhratsky

2016

Phil. Trans. R. Soc. B

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From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Metabolism of ATP required intracellular free Ca 2þ to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca 2þ as a universal signalling molecule. The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca 2þ as a universal signalling ion; similarly, Ca 2þ is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic processes. Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bacterial endosymbionts were a first step for the emergence of complex eukaryotic cells. Simultaneously, Ca 2þ started to be exploited for shortrange signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca 2þ interfere with each other because of the low solubility of calcium phosphates. The need to keep cytosolic Ca 2þ low forced cells to restrict Ca 2þ signals in space and time and to develop energetically favourable Ca 2þ signalling and Ca 2þ microdomains. These steps in tandem dominated further evolution. The ATP molecule (often released by Ca 2þ -regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca 2þ signalling. Similar to atmospheric oxygen, Ca 2þ must have been reverted from a deleterious agent to a most useful (intra-and extracellular) signalling molecule. Invention of intracellular trafficking further increased the role for Ca 2þ homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca 2þ and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story.This article is part of the themed issue 'Evolution brings Ca 2þ and ATP together to control life and death'.

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Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters: evolution and tissue expression

Cited by 57 publications

References 52 publications

Vesicular and conductive mechanisms of nucleotide release

Vesicular and conductive mechanisms of nucleotide release

Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules

Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling

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Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters: evolution and tissue expression

Cited by 57 publications

References 52 publications

Vesicular and conductive mechanisms of nucleotide release

Vesicular and conductive mechanisms of nucleotide release

Vesicular nucleotide transporter regulates the nucleotide content in airway epithelial mucin granules

Inseparable tandem: evolution chooses ATP and Ca2+to control life, death and cellular signalling

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Inseparable tandem: evolution chooses ATP and Ca²⁺to control life, death and cellular signalling