Nutrient availability regulates proline/alanine transporters in Trypanosoma brucei.

Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE

Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology

Alanine/*metabolism ; Amino Acid Transport Systems, Neutral/*metabolism ; Nutrients/*pharmacology ; Trypanosoma brucei brucei/*drug effects ; Trypanosoma brucei brucei/*metabolism; Adaptation, Physiological/drug effects ; Biological Transport/drug effects ; Energy Metabolism/drug effects ; Trypanosoma brucei brucei/physiology

Trypanosoma brucei is a species of unicellular parasite that can cause severe diseases in livestock and humans, including African trypanosomiasis and Chagas disease. Adaptation to diverse environments and changes in nutritional conditions is essential for T. brucei to establish an infection when changing hosts or during invasion of different host tissues. One such adaptation is the ability of T. brucei to rapidly switch its energy metabolism from glucose metabolism in the mammalian blood to proline catabolism in the insect stages and vice versa. However, the mechanisms that support the parasite's response to nutrient availability remain unclear. Using RNAseq and qRT-PCR, we investigated the response of T. brucei to amino acid or glucose starvation and found increased mRNA levels of several amino acid transporters, including all genes of the amino acid transporter AAT7-B subgroup. Functional characterization revealed that AAT7-B members are plasma membrane-localized in T. brucei and when expressed in Saccharomyces cerevisiae supported the uptake of proline, alanine, and cysteine, while other amino acids were poorly recognized. All AAT7-B members showed a preference for proline, which is transported with high or low affinity. RNAi-mediated AAT7-B downregulation resulted in a reduction of intracellular proline concentrations and growth arrest under low proline availability in cultured procyclic form parasites. Taken together, these results suggest a role of AAT7-B transporters in the response of T. brucei to proline starvation and proline catabolism.
Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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Keywords: Trypanosoma brucei; amino acid; amino acid transport; cell metabolism; energy metabolism; gene expression; parasite metabolism; transcriptomics; transporter

0 (Amino Acid Transport Systems, Neutral)
9040-98-6 (proline transporter)
OF5P57N2ZX (Alanine)

Date Created: 20210322 Date Completed: 20210818 Latest Revision: 20240402

20240402

PMC8094907

10.1016/j.jbc.2021.100566

33745971