Nutrient availability regulates proline/alanine transporters in Trypanosoma brucei

Haindrich, Alexander C.; Ernst, Viona; Naguleswaran, Arunasalam; Oliveres, Quentin-Florian; Roditi, Isabel; Rentsch, Doris (2021). Nutrient availability regulates proline/alanine transporters in Trypanosoma brucei. Journal of biological chemistry, 296, p. 100566. American Society for Biochemistry and Molecular Biology 10.1016/j.jbc.2021.100566

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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. RNAimediated 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
08 Faculty of Science > Department of Biology > Institute of Cell Biology
08 Faculty of Science > Department of Biology > Institute of Cell Biology > Parasitologie
08 Faculty of Science > Department of Biology > Institute of Plant Sciences (IPS) > Molecular Plant Physiology
08 Faculty of Science > Department of Biology > Institute of Plant Sciences (IPS)
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

Haindrich, Alexander Christoph, Ernst, Viona Selina, Naguleswaran, Arunasalam, Oliveres, Quentin-Florian Pierre, Roditi, Isabel, Rentsch, Doris

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture
500 Science > 580 Plants (Botany)

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Peter Alfred von Ballmoos-Haas

Date Deposited:

11 Jun 2021 10:31

Last Modified:

05 Dec 2022 15:51

Publisher DOI:

10.1016/j.jbc.2021.100566

PubMed ID:

33745971

BORIS DOI:

10.48350/156277

URI:

https://boris.unibe.ch/id/eprint/156277

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