Protein tyrosine phosphatase TbPTP1: A molecular switch controlling life cycle differentiation in trypanosomes

Balázs Szöor, Jude Wilson, Helen McElhinney, Lydia Tabernero, Keith R. Matthews

    Research output: Contribution to journalArticlepeer-review


    Differentiation in African trypanosomes (Trypanosoma brucei) entails passage between a mammalian host, where parasites exist as a proliferative slender form or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak of each parasitaemia and are committed to differentiation to procyclic forms that inhabit the tsetse midgut. We have identified a protein tyrosine phosphatase (TbPTP1) that inhibits trypanosome differentiation. Consistent with a tyrosine phosphatase, recombinant TbPTP1 exhibits the anticipated substrate and inhibitor profile, and its activity is impaired by reversible oxidation. TbPTP1 inactivation in monomorphic bloodstream trypanosomes by RNA interference or pharmacological inhibition triggers spontaneous differentiation to procyclic forms in a subset of committed cells. Consistent with this observation, homogeneous populations of stumpy forms synchronously differentiate to procyclic forms when tyrosine phosphatase activity is inhibited. Our data invoke a new model for trypanosome development in which differentiation to procyclic forms is prevented in the bloodstream by tyrosine dephosphorylation. It may be possible to use PTP1B inhibitors to block trypanosomatid transmission. © The Rockefeller University Press.
    Original languageEnglish
    Pages (from-to)293-303
    Number of pages10
    JournalJournal of Cell Biology
    Issue number2
    Publication statusPublished - 23 Oct 2006


    Dive into the research topics of 'Protein tyrosine phosphatase TbPTP1: A molecular switch controlling life cycle differentiation in trypanosomes'. Together they form a unique fingerprint.

    Cite this