Nucleotide metabolism is an essential process in all living organisms as nucleotides function as energy providers, signals and building blocks for nucleic acids as well as the plant hormone cytokinin. Nucleotide metabolism can be structured into de novo synthesis, salvage and catabolism with corresponding transport processes. During de novo nucleotide synthesis nucleoside monophosphates are synthesized from amino acids, bicarbonate, organic acids, and phosphoribosyl pyrophosphate (PRPP). In addition, the reducing equivalents adenosine-5′triphosphate (ATP) and tetrahydrofolate (THF) are required (Zrenner et al., 2006). All organisms are capable of performing such nucleotide de novo synthesis. The only known exceptions are human pathogenic protists lacking purine de novo synthesis and compensating for this lack by import of nucleobases or nucleosides from the host cells, which are then recycled to nucleotides by the salvage pathway (Mäser et al., 1999). According to the current view purine nucleotide de novo synthesis is finalized in plastids and the resulting monophosphates have to be delivered to other compartments in which nucleotides are needed.

In the salvage pathway nucleobases can be converted to the corresponding monophosphates by action of phosphoribosyl transferases (PRTs). In addition nucleosides can be phosphorylated by nucleoside kinases (NKs). Both pathways are less energy consuming than de novo synthesis and allow preserving nitrogen and energy in nucleobases and nucleosides. Catabolism of nucleosides and nucleobases allows the liberation of nitrogen in form of ammonia to be reassimilated in the glutamine oxoglutarate aminotransferase (GOGAT) pathway (Jung et al., 2009, 2011; Zrenner et al., 2009; Cornelius et al., 2011; Werner and Witte, 2011). Especially intermediates of purine catabolism such as allantoin and allantoate might exhibit distinct physiological functions such as acting as scavengers for reactive oxygen species (ROS; Brychkova et al., 2008). In some legumes, allantoin and allantoic acid are the main products of nitrogen fixation and serves as the primary nitrogen transport form Christensen and Jochimsen (1983), Smith and Atkins (2002). Accordingly, specialized transporters (ureide permeases) are required for the distribution of ureides in these plant species.

Purine de novo synthesis from PRPP and glutamine (Gln) to inosine monophosphate (IMP) involves nine enzymatic steps (Zrenner et al., 2006). The first enzymatic reaction is catalyzed by the glutamine phosphoribosyl pyrophosphate amidotransferase (ATase) which is encoded by one to four homologous genes in Angiosperm species according to the Phytozome database (Goodstein et al., 2012; www.phytozome.net). In Arabidopsis three ATase genes are present. Knockout of ATase2 is characterized by pale green mosaic leaves, also known as reticulated leaf mutant and a 50% reduction in leaf cell size indicating the role of purine de novo synthesis in cell division (Hung et al., 2004; van der Graaff et al., 2004; Lundquist et al., 2014). All other steps, except for adenylosuccinate lyase which is encoded by two genes, are single copy genes in Arabidopsis (Zrenner et al., 2006). No homozygous mutants for any of these genes are described following the logic that no free living organism can develop without nucleotide de novo synthesis. However, it is not reported whether de novo synthesis is performed in each individual plant cell or if some cells depend on salvage pathway activity and thus on import of corresponding precursors. In early plant development it is supposed that the production of nucleotides mainly depends on purine and pyrimidine salvage rather than de novo synthesis which dominates at later phases (Ashihara, 1983; Ashihara et al., 1997; Stasolla et al., 2003). So far, the only known transporter mediating export of newly synthesized purine nucleotides out of plastids is the Arabidopsis Brittle 1 protein (Kirchberger et al., 2008).

The initial reaction in pyrimidine de novo synthesis is the formation of carbamoyl phosphate by carbamoyl phosphate synthase. This enzyme is composed of two subunits. Mutants in both CarA and CarB were identified in Ven3 and Ven6 and exhibited a reticulate phenotype, which means that the leaf parenchyma cells are chlorotic or degenerated whereas the cells around the vasculature stay green, reviewed in Lundquist et al. (2014). The four subsequently acting proteins aspartate transcarbamoylase (ATCase), dihydroorotase (DHOase), dihydroorotate dehydrogenase (DHODH) and uridine-5′-monophosphate synthase (UMPSase) are encoded by single genes in Arabidopsis, potato and tobacco (Giermann et al., 2002; Zrenner et al., 2006).

Antisense repression of all genes of pyrimidine de novo synthesis in potato and tobacco revealed that about 20% of wildtype transcript levels are sufficient for plant growth. Below this level growth restrictions become apparent. In case of DHOase and ATCase a clear correlation between protein amount and growth could be detected, pointing out the importance of pyrimidine de novo synthesis for plant development (Schröder et al., 2005). The subcellular distribution of de novo synthesis points out the necessity of the plastidic nucleobase transporter PLUTO, described in detail in the chapter “The nucleobase:cation symporter 1 family.”

When nucleosides or nucleobases are imported into a plant cell by one of the many transport proteins present in plants they can undergo two fates. (1) They can be recycled to nucleoside monophosphates by PRTs or NKs. (2) They are subjected to complete degradation by which nitrogen is liberated in form of ammonia and may then be reassimilated to synthesize amino acids. According to the results of the analysis of mutants in catabolic enzymes as well as flux measurements using radiolabeled nucleosides and nucleobases it can be concluded that nucleosides are more effectively salvaged compared to nucleobases. In other words, the hydrolysis of nucleosides to nucleobases by nucleoside hydrolases (NSHs) results in a shift toward catabolism. This allows the assumption that nucleoside import into cells mainly supports salvage whereas nucleobase import supports catabolism.

In the cell relative adenylate contents determine the cellular energy charge whereas outside ATP seems to be the primary signal (Roux and Steinebrunner, 2007; Tanaka et al., 2010; Möhlmann et al., 2013). Such extracellular ATP can result from wounding of cells, export by vesicle flow or by direct transport by PmANT1 (Plasma membrane Adenine Nucleotide Transporter 1; Rieder and Neuhaus, 2011). The sensing of this extracellular ATP is mediated by the recently discovered receptor DORN1 (Does not Respond to Nucleotides 1; Choi et al., 2014).

The removal of the ATP signal is mediated by ATP cleaveage by nucleoside triphosphate diphosphohydrolases (NDPDases) or phosphatases. Which enzymes are in charge for this process has not been clarified so far. However, a complete degradation of ATP down to the nucleobase adenine was shown to proceed in potato tuber apoplastic extracts (Riewe et al., 2008).

In the following sections the different protein families for transport of nucleosides and nucleobases will be described. All members of these families which were characterized at the molecular level including their substrates, expression pattern and physiological function are listed in Tables 1–3.

Equilibrative nucleoside transporters (ENTs) represent a family of integral membrane proteins present in a wide range of eukaryotic organisms and mediating transport of hydrophilic nucleoside substrates. Substantial progress has been made in characterization of mammalian ENTs in the last decades due to their medical importance (Cabrita et al., 2002; Baldwin et al., 2003; King et al., 2006; Young et al., 2013), whereas knowledge about plant ENTs is still limited. First descriptions of plant nucleoside transporters appeared in 2000 and 2001 (Li and Wang, 2000; Möhlmann et al., 2001). In contrast to nucleobase transport, nucleoside transport in plants is mediated by members of just one transporter family: ENTs. Members from four plant species have been characterized at the biochemical level to date – AtENT1, 3, 4, 6, and 7 from Arabidopsis, OsENT2 from rice, HvENT1 from barley and StENT1 and 3 from potato (Table 1). In contrast to mammalian homologs which mediate an equilibrative transport of substrates along a concentration gradient, most plant ENT proteins function as substrate-proton symporters (Li et al., 2003; Wormit et al., 2004; Hirose et al., 2005; Traub et al., 2007). The only known exception so far represents AtENT7 which was shown to catalyze a nucleoside transport in yeast that was hardly affected by the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and the pH value of the medium (Wormit et al., 2004). Nucleoside transport has been studied after heterologous expression of the corresponding genes in yeast and Xenopus oocytes. All five Arabidopsis proteins analyzed so far (AtENT1, AtENT3, AtENT4, AtENT6, and AtENT7) exhibit broad substrate specificity and transport the purine nucleosides adenosine and guanosine, as well as the pyrimidine nucleosides cytidine and uridine. The apparent K_M values were in the range from 3 to 94 μ M (Table 1). Transport was strongly inhibited by deoxynucleosides and to a lesser extent by nucleobases (Möhlmann et al., 2001; Li et al., 2003; Wormit et al., 2004). Typical inhibitors of mammalian ENT proteins, such as dilazep and nitrobenzylmercaptopurine ribonucleoside (NBMPR) surprisingly exerted almost no effect on Arabidopsis ENT proteins.

An AtENT3 mutant was identified as FUR1 and contains a point mutation in the AtENT3 gene which leads to an exchange of glycine to arginine at position 281 and to the loss of function (Wu and King, 1994; Traub et al., 2007). FUR1 mutants and AtENT3 T-DNA mutants are completely resistant against the toxic pyrimidine nucleoside analog 5-fluorouridine (5-FU). This lead to the identification of AtENT3 as the major pyrimidine importer in Arabidopsis seedlings (Chen et al., 2006; Traub et al., 2007). Since NSH3—an extracellular purine specific nucleoside hydrolase—cleaves inosine and adenosine purines can still be imported in form of nucleobases in AtENT3 mutants (Jung et al., 2011). Gene expression of all six AtENTs could be observed during seed germination and development. Whereas the transcript level of AtENT1 remained relatively constant, the transcript of AtENT3, 4, 6, 7, and 8 steadily increased while germination proceeded (Chen et al., 2006). Expression analysis with 10 day old seedlings indicated relatively high transcript levels for AtENT1 and AtENT3 whereas the transcript of all other AtENTs was markedly lower (Cornelius et al., 2012). Furthermore, expressional analysis of 7 week old plants revealed the presence of AtENT1 transcript in root cells, stem, flower and siliques (Li et al., 2003). Promotor GUS stainings supported these findings and indicated high AtENT1 transcript additionally in pollen (Bernard et al., 2011).

Although AtENT1 and AtENT3 are expressed in root cells, only AtENT3 T-DNA mutants showed a reduced uptake of uridine or the cytotoxic uridine analog 5-FU (Li et al., 2003; Traub et al., 2007; Cornelius et al., 2012). The presence of AtENT1 in two independent tonoplast proteome analysis (Jaquinod et al., 2007; Schulze et al., 2012) undermined the belief that AtENT1 is present at the plasma membrane (Li and Wang, 2000). Correlation between overexpression of AtENT1 and lower adenosine and 2′:3′ adenosine monophosphate (2′:3′-cAMP) contents in the vacuole, which appear as breakdown products of vacuolar RNA degradation gave hints for a participation of AtENT1 in transport processes of RNA break down products. As a proton symporter AtENT1 exports nucleosides from the vacuole, leading to the question about the physiological function of such a vacuolar nucleoside transport activity. It has been reported that vacuoles from tomato cell culture contain nucleosides and further RNA breakdown products (Leinhos et al., 1986; Abel et al., 1990). Therefore, one might speculate that RNA degradation partially takes place in the vacuole and AtENT1 is involved in export of liberated nucleosides for salvage or catabolism. Vacuolar RNase isoforms were identified in tomato and Arabidopsis (RNS2; Abel and Glund, 1987; Löffler et al., 1992). Beyond, RNS2 mutants exhibited reduced RNA degradation activity (Hillwig et al., 2011). The same authors provided evidence for an entry of RNA into vacuoles by autophagy.

Four genes coding for potential equilibrative nucleoside transporters were identified in rice, designated OsENT1-4. Analysis in yeast cells expressing OsENT2 revealed high affinity purine and pyrimidine transport (Hirose et al., 2005). Interestingly transport was also affected in the presence of several deoxy-nucleosides and in addition cytokinin type nucleosides (isopentenyl adenine riboside, iPR; trans-zeatin riboside, tZR) were transported (Hirose et al., 2005). Therefore, OsENT2 represents a nucleoside transporter in rice with a broad substrate spectrum. In addition, direct evidence for a participation of Arabidopsis ENT6 in cytokinin nucleoside transport with a preference for iPR was gained (Hirose et al., 2008). Furthermore, Sun et al. (2005) were able to provide indications for an involvement of AtENT3 and AtENT8 in cytokinin transport. However, whether these data reflect a participation of ENT proteins in cytokinin metabolism in vivo has to be elucidated.

A number of membrane protein families mediating intra- and intercellular transport of nucleobases are known to date. New findings expand their physiological role to include plant cytokinin and alkaloid metabolism as well as metabolism of vitamin B6.

Purine permease transporters (PUPs) belong to a family of small, highly hydrophobic membrane proteins. They are related to nucleotide-sugar transporters known from bacteria, archae, fungi and diverse eukaryotes within the drug metabolite transporter (DMT) super family (Jelesko, 2012). Homologs have been identified in several plant species like Arabidopsis, banana, rice, maize, tobacco and tomato (Gillissen et al., 2000; Hildreth et al., 2011; Goodstein et al., 2012; Jelesko, 2012). In Arabidopsis 21 PUP-like proteins are present with 9–10 transmembrane helices based on multiple prediction tools (Schwacke et al., 2003). The first member of the purine permease transporter family AtPUP1 was identified by complementation of a yeast mutant deficient in adenine uptake (fcy2) with an Arabidopsis cDNA expression library (Gillissen et al., 2000). To date, only AtPUP1, AtPUP2, AtPUP3, and NtNUP1, a tobacco PUP-like homolog, have been biochemically characterized. Direct uptake measurements demonstrated that AtPUP1 is able to transport adenine, trans-zeatin and pyridoxine (PN)—one of the three compounds that can be called vitamin B6 (Gillissen et al., 2000; Bürkle et al., 2003; Szydlowski et al., 2013). Moreover, competition studies and yeast complementation studies suggest additional transport abilities for kinetin, caffeine, cytosine, hypoxanthine, nicotine and the vitamin B6 forms pyridoxal (PL) and pyridoxamine (PM). The transport is supposed to work as a substrate-proton symport (Gillissen et al., 2000; Bürkle et al., 2003; Szydlowski et al., 2013). As well as AtPUP1, AtPUP2 mediated a proton-coupled adenine transport with the ability of trans-zeatin, cis-zeatin, kinetin, isopentenyladenine and benzylaminopurine transport (Bürkle et al., 2003). Moreover, direct uptake measurements with radiolabeled PN showed a weak import activity for AtPUP2 in yeast. In contrast, no substrate of AtPUP3 was identified so far (Bürkle et al., 2003). Uptake assays with radiolabeled substrates demonstrated that NtNUP1 from tobacco is able to transport nicotine but determination of kinetics weren't successful due to nicotine toxicity. However, kinetin atropine, anatabine, or anabasine added as competitors did not efficiently compete for nicotine uptake (Hildreth et al., 2011). Beyond, adenine is no substrate for NtNUP1 which indicates a high nicotine specificity (Hildreth et al., 2011). Arabidopsis seedlings expressing the AtPUP1-YFP fusion protein as well as transient expression studies of NtNUP1-GFP in tobacco mesophyll cells exhibited fluorescence at the plasma membrane, suggesting that NtNUP1 and AtPUP1 import apoplastic metabolites into the cell (Hildreth et al., 2011; Szydlowski et al., 2013). The subcellular localization of other PUP members remains unclear. In organ specific expression data for the AtPUP-like family from the Genevestigator database (Zimmermann et al., 2004), only a subset of 12 AtPUPs was represented (Cedzich et al., 2008). AtPUP1, AtPUP4, AtPUP11, AtPUP14, and AtPUP18 showed high expression levels throughout all tissues, whereas AtPUP2 and seven other members were only expressed at lower levels (Zimmermann et al., 2004; Cedzich et al., 2008). AtPUP1 is expressed in cotyledons, the stigma surface of siliques and epithem cells of hydatodes. In the epithem the transporter may play a role in retrieval of solutes from the xylem sap like purines, cytokinins or vitamin B6 (Bürkle et al., 2003; Hirose et al., 2008; Szydlowski et al., 2013). Arabidopsis cells possess a high affinity cytokinin transport system which shares properties with AtPUP1 and is compatible with the observed concentration range for cytokinins in xylem sap (Weiler and Ziegler, 1981; Komor et al., 1993; Beck and Wagner, 1994; Takei et al., 2001; Cedzich et al., 2008). However, the most prominent cytokinin form in xylem sap is tZ ribose, but also tZ is present and can be imported into the cells via AtPUP1 in general (Hirose et al., 2008). AtPUP1 T-DNA mutants showed altered vitamin B6 composition of the guttation sap. The PN and PL contents were significantly increased by 253 and 64%, respectively compared to wildtype (Szydlowski et al., 2013). However, there is no information about alterations in purine or cytokinin content in those mutants, so the physiological relevance of AtPUP1 in purine and cytokinin recycling from the guttation sap remains unclear. Nevertheless, the scavenging of solutes from the xylem sap by AtPUP1 is an example of the plants effort to recycle valuable compounds and conserve energy. AtPUP2 promoter expression was found in the vascular system of leaves and was limited to the phloem, indicating a potential role in phloem loading whereupon multiple transporters are required for long-distance transport. Other members of the AtPUP-like family are potential candidates to address this role (Bürkle et al., 2003; Jelesko, 2012). In AtPUP3-promotor-GUS plants, the staining was restricted to pollen, so AtPUP3 could mediate important transport processes of purines and cytokinins during pollen germination and tube elongation (Bürkle et al., 2003).

Ureide permeases (UPSs) form a protein superfamily of plant membrane transporters with five members in Arabidopsis, whereas three of them (AtUPS1, AtUPS2, and AtUPS5) have been characterized. The name originated from the ability of AtUPS1 to complement a yeast mutant defective in allantoin uptake (Desimone et al., 2002). Homologous proteins are present in legumes like french bean (PvUPS1) and soybean (GmUPS1-1 and GmUPS1-2), where ureides like allantoin and allantoic acid serve as long-distance transport molecules, representing up to 90% of the transported nitrogen (Desimone et al., 2002; Smith and Atkins, 2002). However, non-legumes like Arabidopsis use mainly amino acids, nitrate but also nucleosides and nucleobases like uracil in small amounts for long distance transport of nitrogen (Schmidt et al., 2004).

The nucleobase:cation symporter 1 (NCS1) family consists of over 1000 proteins from bacteria, archaea, yeast, fungi and plants. Also known as purine-related transporters, they generally transport purines in a proton symport mode and consist of 12 transmembrane domains (TMs; Saier et al., 2009; www.tcdb.org). The uridine transporter FUI1 and the uracil transporter FUR4 from Saccharomyces cerevisiae (Chevallier and Lacroute, 1982; Zhang et al., 2006), the benzyl-hydantoin transporter MHP1 from Microbacterium liquefaciens (Weyand et al., 2008) and the cytosine- purine transporter FCYB from Aspergillus nidulans (Krypotou et al., 2012) are examples for well-studied NCS1 proteins.

In Arabidopsis, the plastidic nucleobase transporter PLUTO was identified as the sole NCS1 member with 23% sequence identity to FUR4. Other plants like maize (Zea mays), rice (Oryza sativa), wine (Vitis vinifera) and poplar (Populus trichocarpa) also possess a PLUTO homolog while Brachypodium distachyon even harbors two PLUTO homologs (Schwacke et al., 2003; Witz et al., 2014). Quite recently, a PLUTO homolog was also identified in Clamydomonas reinhardtii which is capable of transporting uracil, adenine, guanine, and allantoin suggesting that the solute specificity for plant NCS1 occurred early in plant evolution and is distinct from solute transport specificities of single cell fungal NCS1 proteins (Schein et al., 2013).

The nucleobase-ascorbate transporter (NAT) family, belonging to the nucleobase:cation symporter 2 (NCS2) family, represents the largest and most conserved class of nucleobase transporters (De Koning and Diallinas, 2000). It includes more than 2000 putative members in all major taxa of organisms like eubacteria, archea, filamentous fungi, plants, insects, nematodes, mammals and humans (De Koning and Diallinas, 2000; Frillingos, 2012). Remarkably, most protozoa and Saccharomyces cerevisiae do not possess NAT proteins and only a few NAT proteins have been biochemically characterized so far (Frillingos, 2012). Transporters of known function are for example UapA and UapC from Aspergillus nidulans (Diallinas et al., 1995), UraA from Escherichia coli (Andersen et al., 1995; Lu et al., 2011), PyrP from Bacillus subtilis (Turner et al., 1994), Lpe1 from Zea mays (Argyrou et al., 2001) or the mammalian transporters rSNBT (Yamamoto et al., 2009), SVCT1 and SVCT2 (Tsukaguchi et al., 1999). These transporters are very specific for the cellular uptake of either uracil, xanthine or uric acid (bacteria, fungi, plants) or ascorbate (mammalians; Frillingos, 2012). NAT proteins usually consist of 400–650 amino acids and 12–14 transmembrane segments. Moreover, a common feature is the existence of the NAT-signature upstream from transmembrane segment 9 (Koukaki et al., 2005) and a QH-motif in transmembrane segment 1 (Pantazopoulou and Diallinas, 2007). Both motifs are highly conserved among NAT proteins and necessary for a proper function of UapA, UapC, or YgfO from Aspergillus nidulans (Gournas et al., 2008).

In Arabidopsis 12 members of the NAT family, AtNAT1-12, have been identified and analyzed concerning their expression patterns during growth and development (Maurino et al., 2006). Based on a multiple sequence alignment, the AtNAT proteins split into five clades which correlates with their expression during the life cycle of Arabidopsis (Maurino et al., 2006). Some of the members of this gene family show ubiquitous expression (e.g., AtNAT12), while the expression of other AtNAT genes is restricted to specific tissues (AtNAT7, AtNAT8, AtNAT9; Maurino et al., 2006; Table 3). In addition, most AtNATs show pronounced expression is vascular tissues, indicating that these proteins might have a function in long-distance transport of metabolites (Maurino et al., 2006). All analyzed mutant lines of AtNAT family members including several double- and triple mutants belonging to the same clade lack obvious phenotypical differences compared to the wild type. These observations might be due to a high redundancy of NAT functions in plants. Either the functions can be compensated by other NAT genes or by other nucleobase transporters (Maurino et al., 2006). Transient expression studies of AtNAT-GFP fusion constructs in different systems showed that AtNAT7, AtNAT8 and also AtNAT12 are located to the plasma membrane (Maurino et al., 2006), although AtNAT12 possesses a hydrophilic N-terminus with a prediction for a localization in the chloroplast (Schwacke et al., 2003).

The biochemical characterization of these proteins was not successful by the complementation of Aspergillus nidulans strains lacking functional NATs, heterologous expression studies in yeast, oocytes or measurements of radiolabeled substrates in whole plants (Maurino et al., 2006). Quite recently, the heterologous expression of AtNAT3 and AtNAT12 in E. coli cells lacking the endogenous uracil transporter UraA allowed for a detailed biochemical characterization of these two NAT proteins showing that they mediate high affinity uptake of uracil, adenine and guanine (Niopek-Witz et al., 2014).

The AzgA proteins define a group of membrane proteins which may be distantly related to the NAT family and homologs of unknown function are found in plants, fungi, bacteria and Archaea. In Aspergillus nidulans, AzgA has been identified as a proton-symporter specific for hypoxanthine, guanine, and adenine (Cecchetto et al., 2004). Two proteins with significant similarity to the AzgA adenine-guanine-hypoxanthine transporter of Aspergillus nidulans, namely AtAzg1 and AtAzg2, have also been identified in Arabidopsis. These proteins share 36.5 and 38.5% identical amino acids with AzgA, respectively (Mansfield et al., 2009). Homozygous mutant lines of the allele AtAzg1-1 and AtAzg1-2 showed increased resistance on 8-azaguanine and 8-azaadenine compared to the wildtype and this effect was even more pronounced in AtAzg1 and AtAzg2 double mutants. Growth tests of S. cerevisiae cells expressing AtAzg1 and AtAzg2 on medium supplemented with the toxic analogs 8-azaadenine or 8-azaguanine as well as direct uptake studies with radiolabeled [³H]-adenine and [³H]-guanine indicated that AtAzg1 and AtAzg2 are capable of transporting adenine and guanine (Mansfield et al., 2009). Both proteins are integral membrane proteins with 10 transmembrane segments and a prediction for a localization in chloroplasts (Schwacke et al., 2003). However, there is no experimental evidence for a localization of AtAzg proteins in the chloroplast envelope. Mansfield et al. (2009) suggested that AtAzg1 is located to the plasma membrane necessary for adenine and guanine import while AtAzg2 might be located to the plastidic envelope based on the predicted targeting motif. However, several prediction tools reveal a chloroplastidic localization to be more likely for AtAzg1 rather than for AtAzg2 (Schwacke et al., 2003).

In the last years it became apparent that nucleoside and nucleobase transporters accept a diverse range of substrates, far more than judged by the given name of these proteins. Consequently, the adjudicated physiological functions also increased. To briefly summarize, ENTs represent the sole family of nucleoside transporters in plants, mediating transport of purine and pyrimidine nucleosides across the plasma membrane and the tonoplast. Within the large number of nucleobase transport families, PUPs exhibit a broad substrate spectrum including purine nucleobases, cytokinins, vitamins and alkaloids. UPS proteins play a major role in ureide long distance transport in tropical legumes whereas in non-legumes pyrimidine nucleobase transport predominates. From the NCS1 protein family only one member is present in higher plants with PLUTO, the plastidic nucleobase transporter. In contrast, NCS2 members reside at the plasma membrane where they catalyze transport of purine and pyrimidine nucleobases. It can be anticipated that research in the field of nucleoside and nucleobase transport will continue to develop fruitfully in future, implementing aspects from crop plants.