Fungal nucleobase transporters

Abstract

Early genetic and physiological work in bacteria and fungi has suggested the presence of highly specific nucleobase transport systems. Similar transport systems are now known to exist in algae, plants, protozoa and metazoa. Within the last 15 years, a small number of microbial genes encoding nucleobase transporters have been cloned and studied in great detail. The sequences of several other putative proteins submitted to databases are homologous to the microbial nucleobase transporters but their physiological functions remain largely undetermined. In this review, genetic, biochemical and molecular data are described concerning mostly the nucleobase transporters of Aspergillus nidulans and Saccharomyces cerevisiae, the two model ascomycetes from which the great majority of data come from. It is also discussed as to what is known on the nucleobase transporters of the two most significant pathogenic fungi: Candida albicans and Aspergillus fumigatus. Apart from highlighting how a basic process such as nucleobase recognition and transport operates, this review intends to highlight features that might be applicable to antifungal pharmacology.

Genetic and molecular characterization reveals a unique nucleobase cation symporter 1 in Arabidopsis

“…1A) [15,16,27,28]. Secondary structure predictions suggest that AtNCS1 and a closely related orthologous protein from Vitus vinifera, are membrane localized proteins showing twelve predicted membrane spanning domains (Fig.…”

“…The remaining four nucleobase transporter families have orthologs in other prokaryotic and eukaryotic taxa. Nucleobase-ascorbate transporters (NATs) are ubiquitous and collectively transport an array of solutes including purines, oxidized purines (xanthine, hypoxanthine, and uric acid), uracil and ascorbate [15,16]. Although none of the 12 identified Arabidopsis NAT loci are functionally-characterized yet, the maize Leaf Permease 1 is known to transport xanthine and uric acid [17,18].…”

The solute specificity profiles of nucleobase cation symporter 1 (NCS1) from Zea mays and Setaria viridis illustrate functional flexibility

“…In contrast to plant genomes, that contain one or two NCS1 loci, fungal genomes contain multiple NCS1 loci (Goodstein et al 2012;Pantazopoulou and Diallinas 2007;Hamari et al 2009). Most research has focused on fungal NCS1 in Saccharomyces cerevisiae and Aspergillus nidulans.…”

“…The remaining three nucleobase transporter families have orthologues among prokaryotes and eukaryotes. Nucleobaseascorbate transporters (NAT) are ubiquitous across taxa and collectively transport a large array of solutes including oxidized purines xanthine and uric acid, uracil, and ascorbate (De Koning and Diallinas 2000;Maurino et al 2006;Pantazopoulou and Diallinas 2007;Gournas et al 2008). The function of plant NATs varies, with two of twelve Arabidopsis NAT transporting adenine, guanine, and uracil (Niopek-Witz et al 2014), while the maize NAT leaf permease 1 transports xanthine and uric acid (Schultes et al 1996;Argyrou et al 2001).…”

Heterologous complementation studies reveal the solute transport profiles of a two-member nucleobase cation symporter 1 (NCS1) family in Physcomitrella patens

“…NCS1 proteins sort into two different sub-families based upon amino acid sequence similarity: the FUR4-like and the FCY2-like NCS1, named after the Saccharomyces cerevisiae FUR4 uracil transporter and FCY2 adenine, guanine, cytosine transporter, respectively (Pantazopoulou and Diallinas, 2007). Upon amino acid sequence similarity and phylogenetic analysis Viridiplantae NCS1 always clade with FUR4-like subfamily (Mourad et al, 2012;Schein et al, 2013;Ma et al, 2013), although horizontal transfer of NCS1 into plants seems to stem from bacterial rather than fungal origins (Yue et al, 2012).…”