Independent Pathways Can Transduce the Life-Cycle Differentiation Signal in Trypanosoma brucei

Szöőr, Balazs, Dyer, Naomi, Ruberto, Irene, Acosta Serrano, Alvaro ORCID: https://orcid.org/0000-0002-2576-7959 and Matthews, Keith R. (2013) 'Independent Pathways Can Transduce the Life-Cycle Differentiation Signal in Trypanosoma brucei'. PLoS Pathogens, Vol 9, Issue 10, e1003689.

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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.

Item Type:	Article
Subjects:	QU Biochemistry > Enzymes > QU 136 Hydrolases QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins QX Parasitology > QX 45 Host-parasite relations QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors QX Parasitology > Protozoa > QX 70 Mastigophora. (e.g., Giardia. Trichomonas. Trypanosoma. Leishmania) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 705 Trypanosomiasis
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.ppat.1003689
Depositing User:	Martin Chapman
Date Deposited:	18 Feb 2015 15:03
Last Modified:	27 Sep 2019 15:29
URI:	https://archive.lstmed.ac.uk/id/eprint/4930

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