Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.

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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Balazs Szöőr, Naomi A Dyer, Irene Ruberto, Alvaro Acosta-Serrano, Keith R Matthews
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
Materias:
Acceso en línea:https://doaj.org/article/80c2c4c388114e0ca043abd07886144f
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:80c2c4c388114e0ca043abd07886144f
record_format dspace
spelling oai:doaj.org-article:80c2c4c388114e0ca043abd07886144f2021-11-18T06:07:27ZIndependent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.1553-73661553-737410.1371/journal.ppat.1003689https://doaj.org/article/80c2c4c388114e0ca043abd07886144f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24146622/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374African 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.Balazs SzöőrNaomi A DyerIrene RubertoAlvaro Acosta-SerranoKeith R MatthewsPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003689 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Balazs Szöőr
Naomi A Dyer
Irene Ruberto
Alvaro Acosta-Serrano
Keith R Matthews
Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
description 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.
format article
author Balazs Szöőr
Naomi A Dyer
Irene Ruberto
Alvaro Acosta-Serrano
Keith R Matthews
author_facet Balazs Szöőr
Naomi A Dyer
Irene Ruberto
Alvaro Acosta-Serrano
Keith R Matthews
author_sort Balazs Szöőr
title Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
title_short Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
title_full Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
title_fullStr Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
title_full_unstemmed Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.
title_sort independent pathways can transduce the life-cycle differentiation signal in trypanosoma brucei.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/80c2c4c388114e0ca043abd07886144f
work_keys_str_mv AT balazsszoor independentpathwayscantransducethelifecycledifferentiationsignalintrypanosomabrucei
AT naomiadyer independentpathwayscantransducethelifecycledifferentiationsignalintrypanosomabrucei
AT ireneruberto independentpathwayscantransducethelifecycledifferentiationsignalintrypanosomabrucei
AT alvaroacostaserrano independentpathwayscantransducethelifecycledifferentiationsignalintrypanosomabrucei
AT keithrmatthews independentpathwayscantransducethelifecycledifferentiationsignalintrypanosomabrucei
_version_ 1718424550443581440