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Comparative genomics and functional analysis of the NiaP family uncover nicotinate transporters from bacteria, plants, and mammals

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Abstract

The transporter(s) that mediate uptake of nicotinate and its N-methyl derivative trigonelline are not known in plants, and certain mammalian nicotinate transporters also remain unidentified. Potential candidates for these missing transporters include proteins from the ubiquitous NiaP family. In bacteria, niaP genes often belong to NAD-related regulons, and genetic evidence supports a role for Bacillus subtilis and Acinetobacter baumannii NiaP proteins in uptake of nicotinate or nicotinamide. Other bacterial niaP genes are, however, not in NAD-related regulons but cluster on the chromosome with choline-related (e.g., Ralstonia solanacearum and Burkholderia xenovorans) or thiamin-related (e.g., Thermus thermophilus) genes, implying that they might encode transporters for these compounds. Radiometric uptake assays using Lactococcus lactis cells expressing NiaP proteins showed that B. subtilis, R. solanacearum, and B. xenovorans NiaP transport nicotinate via an energy-dependent mechanism. Likewise, NiaP proteins from maize (GRMZM2G381453, GRMZM2G066801, and GRMZM2G081774), Arabidopsis (At3g13050), and mouse (SVOP) transported nicotinate; the Arabidopsis protein also transported trigonelline. In contrast, T. thermophilus NiaP transported only thiamin. None of the proteins tested transported choline or the thiazole and pyrimidine products of thiamin breakdown. The maize and Arabidopsis NiaP proteins are the first nicotinate transporters reported in plants, the Arabidopsis protein is the first trigonelline transporter, and mouse SVOP appears to represent a novel type of mammalian nicotinate transporter. More generally, these results indicate that specificity for nicotinate is conserved widely, but not absolutely, among pro- and eukaryotic NiaP family proteins.

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Acknowledgments

This work was supported in part by US National Science Foundation award # IOS-1025398 (to A.D.H.), by Swiss National Science Foundation grant 31003A_127340 (to D.R.), and by an endowment from the C. V. Griffin, Sr. Foundation. The work of D.A.R. and A.L.O. was supported by the U.S. Department of Energy (DOE) Office of Biological and Environmental Research (BER), as part of BER’s Genomic Science Program (GSP) originating Foundational Scientific Focus Area (FSA) at the Pacific Northwest National Laboratory (PNNL). The work of D.A.R was also supported by award R01GM077402 from the National Institute of General Medical Sciences. We thank Dr. Edmund Kunji for his generous advice and encouragement, and M. Ziemak for technical support.

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Authors and Affiliations

  1. Horticultural Sciences Department, University of Florida, Gainesville, FL, 32611, USA

    Linda Jeanguenin & Andrew D. Hanson

  2. Food Science and Human Nutrition Department, University of Florida, Gainesville, FL, 32611, USA

    Aurora Lara-Núñez & Jesse F. Gregory III

  3. Burnham Institute for Medical Research, La Jolla, CA, 92037, USA

    Dmitry A. Rodionov & Andrei L. Osterman

  4. Institute of Plant Sciences, University of Bern, 3013, Bern, Switzerland

    Nataliya Y. Komarova & Doris Rentsch

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  1. Linda Jeanguenin
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Correspondence to Andrew D. Hanson.

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Linda Jeanguenin and Aurora Lara-Núñez contributed equally to this work.

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Jeanguenin, L., Lara-Núñez, A., Rodionov, D.A. et al. Comparative genomics and functional analysis of the NiaP family uncover nicotinate transporters from bacteria, plants, and mammals. Funct Integr Genomics 12, 25–34 (2012). https://doi.org/10.1007/s10142-011-0255-y

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