A Call for Systematic Research on Solute Carriers

César-Razquin, Adrián; Snijder, Berend; Frappier‐Brinton, Tristan; Isserlin, Ruth; Gyimesi, Gergely; Bai, Xiaoyun; Reithmeier, Reinhart A.F.; Hepworth, David; Hediger, Matthias A.; Edwards, A.M.; Superti‐Furga, Giulio

doi:10.1016/j.cell.2015.07.022

Cited by 514 publications

(519 citation statements)

References 86 publications

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“…These genes are part of a large family essential for transferring solutes across membranes (reviewed in [81][82][83]). Another member of this family, Solute carrier family 2 member 9 (Slc2A9), has been found to be undergoing positive selection in studies on kidney transcriptomes of cactus mouse [41] and of other desert rodents [32].…”

Section: Discussionmentioning

confidence: 99%

“…Slc38a5 and Slc45a3 are among the highly expressed genes in the WET group (they have lower expression in the DRY group); these two solute carriers are members of a large protein family that is responsible for crossmembrane solute transport (reviewed in [81][82][83]). Slc38a5 is involved in sodium-dependent amino-acid (Fig.…”

Section: Differential Gene and Transcript Expression Analysesmentioning

confidence: 99%

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Characterizing the reproductive transcriptomic correlates of acute dehydration in males in the desert-adapted rodent,Peromyscus eremicus

Kordonowy

MacManes

2016

Preprint

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Background: The understanding of genomic and physiological mechanisms related to how organisms living in extreme environments survive and reproduce is an outstanding question facing evolutionary and organismal biologists. One interesting example of adaptation is related to the survival of mammals in deserts, where extreme water limitation is common. Research on desert rodent adaptations has focused predominantly on adaptations related to surviving dehydration, while potential reproductive physiology adaptations for acute and chronic dehydration have been relatively neglected. This study aims to explore the reproductive consequences of acute dehydration by utilizing RNAseq data in the desert-specialized cactus mouse (Peromyscus eremicus). Results: We exposed 22 male cactus mice to either acute dehydration or control (fully hydrated) treatment conditions, quasimapped testes-derived reads to a cactus mouse testes transcriptome, and then evaluated patterns of differential transcript and gene expression. Following statistical evaluation with multiple analytical pipelines, nine genes were consistently differentially expressed between the hydrated and dehydrated mice. We hypothesized that male cactus mice would exhibit minimal reproductive responses to dehydration; therefore, this low number of differentially expressed genes between treatments aligns with current perceptions of this species' extreme desert specialization. However, these differentially expressed genes include Insulin-like 3 (Insl3), a regulator of male fertility and testes descent, as well as the solute carriers Slc45a3 and Slc38a5, which are membrane transport proteins that may facilitate osmoregulation. Conclusions: These results suggest that in male cactus mice, acute dehydration may be linked to reproductive modulation via Insl3, but not through gene expression differences in the subset of other a priori tested reproductive hormones. Although water availability is a reproductive cue in desert-rodents exposed to chronic drought, potential reproductive modification via Insl3 in response to acute water-limitation is a result which is unexpected in an animal capable of surviving and successfully reproducing year-round without available external water sources. Indeed, this work highlights the critical need for integrative research that examines every facet of organismal adaptation, particularly in light of global climate change, which is predicted, amongst other things, to increase climate variability, thereby exposing desert animals more frequently to the acute drought conditions explored here.

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Section: Discussionmentioning

confidence: 99%

Section: Differential Gene and Transcript Expression Analysesmentioning

confidence: 99%

Characterizing the reproductive transcriptomic correlates of acute dehydration in males in the desert-adapted rodent,Peromyscus eremicus

Kordonowy

MacManes

2016

Preprint

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“…Still, there are numerous poorly characterized ABC and SLC transporters with unknown function. A major goal is on the one hand to deorphanize these transporters and evaluate their contribution to interindividual variability of drug response, but on the other hand to understand the involvement in pathophysiology and exploit their potential as drug targets [2].…”

Section: Expert Opinionmentioning

confidence: 99%

“…The SLC superfamily comprises uptake as well as efflux transporters [2]. In contrast, members of the ABC transporter family are predominantly efflux transporters [3].…”

Section: Introductionmentioning

confidence: 99%

The importance of drug transporter characterization to precision medicine

Fisel

Nies

Schaeffeler

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

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“…Besides the uptake of nutrients and ions, some of these transporters are actively involved in the influx of drugs for treating various illnesses. At least 12 of the transporters are specifically involved in the transport of drugs approved by the Food and Drug Administration (FDA), e.g, SLC6A3 transports methylphenidate used for treating psychiatric disorders [11]. In addition, a few of the solute carriers have been shown to mediate uptake of anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%