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The AMPK?1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei.

ABSTRACT: During infection in mammals, the protozoan parasite Trypanosoma brucei transforms from a proliferative bloodstream form to a quiescent form that is pre-adapted to host transition. AMP analogs are known to induce quiescence and also inhibit TbTOR4. To examine the role of AMP-activated kinase (AMPK) in the regulation of this developmental transition, we characterized trypanosome TbAMPK complexes. Expression of a constitutively active AMPK?1 induces quiescence of the infective form, and TbAMPK?1 phosphorylation occurs during differentiation of wild-type pleomorphic trypanosomes to the quiescent stumpy form in vivo. Compound C, a well-known AMPK inhibitor, inhibits parasite differentiation in mice. We also provide evidence linking oxidative stress to TbAMPK?1 activation and quiescent differentiation, suggesting that TbAMPK?1 activation balances quiescence, proliferation, and differentiation.

SUBMITTER: Saldivia M

PROVIDER: S-EPMC5074416 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei.

Saldivia Manuel M Ceballos-Pérez Gloria G Bart Jean-Mathieu JM Navarro Miguel M

Cell reports 20161001 3

During infection in mammals, the protozoan parasite Trypanosoma brucei transforms from a proliferative bloodstream form to a quiescent form that is pre-adapted to host transition. AMP analogs are known to induce quiescence and also inhibit TbTOR4. To examine the role of AMP-activated kinase (AMPK) in the regulation of this developmental transition, we characterized trypanosome TbAMPK complexes. Expression of a constitutively active AMPKα1 induces quiescence of the infective form, and TbAMPKα1 ph ...[more]

PMID: 27732844

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