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

PLoS Pathogens

Irene Ruberto¹  Balazs Szöőr¹  Alvaro Acosta-Serrano²  Naomi A. Dyer²  Keith R. Matthews³ 

[1] Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom;Parasitology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom;Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom

关键词: Trypanosoma;    Cell differentiation;    Phosphorylation;    Proteases;    Tsetse fly;    RNA interference;    Glucose metabolism;    Horses;   

DOI  :  10.1371/journal.ppat.1003689

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY