title: Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
abstract: African trypanosomes cause disease in humans and livestock, generating significant health and welfare problems throughout sub-Saharan Africa. When ingested in a tsetse fly bloodmeal, trypanosomes must detect their new environment and initiate the developmental responses that ensure transmission. The best-established environmental signal is citrate/cis aconitate (CCA), this being transmitted through a protein phosphorylation cascade involving two phosphatases: one that inhibits differentiation (TbPTP1) and one that activates differentiation (TbPIP39). Other cues have been also proposed (mild acid, trypsin exposure, glucose depletion) but their physiological relevance and relationship to TbPTP1/TbPIP39 signalling is unknown. Here we demonstrate that mild acid and CCA operate through TbPIP39 phosphorylation, whereas trypsin attack of the parasite surface uses an alternative pathway that is dispensable in tsetse flies. Surprisingly, glucose depletion is not an important signal. Mechanistic analysis through biophysical methods suggests that citrate promotes differentiation by causing TbPTP1 and TbPIP39 to interact.
authors.affiliation: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Balazs
authors.initials: B
authors.lastname: Szöőr
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Dyer
authors.forename: Irene
authors.initials: I
authors.lastname: Ruberto
authors.forename: Alvaro
authors.initials: A
authors.lastname: Acosta-Serrano
authors.forename: Keith R
authors.initials: KR
authors.lastname: Matthews
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*; D014353:Trypanosomiasis, African / Q000235:genetics / Q000378:metabolism*; D014370:Tsetse Flies / Q000469:parasitology*
chemical_list: D015800:Protozoan Proteins; D010749:Phosphoprotein Phosphatases; D005947:Glucose