Abstract
Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes.
Highlights
Trypanosoma brucei is a protozoan pathogen, which threatens thousands of people and kills millions of farm animals in sub-Saharan Africa [1]
Trypanosoma brucei is a member of a large group of flagellated protozoan parasites that threatens the lives and husbandry of millions of people worldwide
Trypanosomes differentiate from the bloodstream form (BSF) in the mammalian host to the procyclic form (PF), which is adapted to live in the insect vector
Summary
Trypanosoma brucei is a protozoan pathogen, which threatens thousands of people and kills millions of farm animals in sub-Saharan Africa [1]. There has been substantial progress in understanding the differentiation process of trypanosomes after several groups analyzed changes in transcription profiles during this process ([9,10] reviewed in [11]). It has to be taken into account that trypanosomes regulate steady-state protein levels mainly by posttranscriptional mechanisms [12]. Because translation efficiency can vary up to 100-fold between individual genes, substantial differences in the level of ribosome-bound mRNAs for the same transcripts were detected in different life cycle stages These experiments demonstrate that translational control regulates protein abundance to a similar extent as RNA stability. Careful dissection of the phenotype of DOT1B-depleted parasites suggests a function in chromatin remodeling during developmental differentiation
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