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L-Glutamine uptake is developmentally regulated and is involved in metacyclogenesis in Trypanosoma cruzi.

Abstract：

:Trypanosoma cruzi, the aetiological agent of Chagas disease, can obtain L-glutamine (Gln) through the enzyme glutamine synthetase (GS) using glutamate (Glu) and ammonia as substrates. In this work, we show additional non-canonical roles for this amino acid: its involvement in ATP maintenance and parasite survival under severe metabolic stress conditions and its participation in the differentiation process occurring in the insect vector (metacyclogenesis). These roles are dependent on the supply of Gln from an extracellular source. We show that T. cruzi incorporates Gln through a saturable and specific transport system, which results in unusual stability at elevated temperatures. The activity was moderately higher at pH values between 6 and 7 and was sensitive to the dissipation of the H+ gradient at the plasma membrane. When analysed in the different life cycle stages, we found that Gln transport is developmentally regulated. In fact, Gln uptake and GS activity seem to be finely regulated at most stages: when GS activity is increased, transport is decreased and vice versa, with the exception of trypomastigotes, where both sources of Gln are diminished. This metabolic adaptation reflects the relevance of Gln in T. cruzi biology and the plasticity of these parasites to adjust their metabolism to changing environments.

journal_name

Mol Biochem Parasitol

journal_title

Molecular and biochemical parasitology

authors

Damasceno FS,Barisón MJ,Crispim M,Souza ROO,Marchese L,Silber AM

doi

10.1016/j.molbiopara.2018.07.007

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

17-25

eissn

0166-6851

issn

1872-9428

pii

S0166-6851(18)30052-5

journal_volume

224

pub_type

杂志文章

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