An Alba-domain protein required for proteome remodelling during trypanosome differentiation and host transition

Bevkal, Shubha; Naguleswaran, Arunasalam; Rehmann, Ruth; Kaiser, Marcel; Heller, Manfred; Roditi, Isabel (2021). An Alba-domain protein required for proteome remodelling during trypanosome differentiation and host transition. PLoS pathogens, 17(1), e1009239. Public Library of Science 10.1371/journal.ppat.1009239

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The transition between hosts is a challenge for digenetic parasites as it is unpredictable. For Trypanosoma brucei subspecies, which are disseminated by tsetse flies, adaptation to the new host requires differentiation of stumpy forms picked up from mammals to procyclic forms in the fly midgut. Here we show that the Alba-domain protein Alba3 is not essential for mammalian slender forms, nor is it required for differentiation of slender to stumpy forms in culture or in mice. It is crucial, however, for the development of T. brucei procyclic forms during the host transition. While steady state levels of mRNAs in differentiating cells are barely affected by the loss of Alba3, there are major repercussions for the proteome. Mechanistically, Alba3 aids differentiation by rapidly releasing stumpy forms from translational repression and stimulating polysome formation. In its absence, parasites fail to remodel their proteome appropriately, lack components of the mitochondrial respiratory chain and show reduced infection of tsetse. Interestingly, Alba3 and the closely related Alba4 are functionally redundant in slender forms, but Alba4 cannot compensate for the lack of Alba3 during differentiation from the stumpy to the procyclic form. We postulate that Alba-domain proteins play similar roles in regulating translation in other protozoan parasites, in particular during life-cycle and host transitions.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bevkal Subramanyaswamy, Shubha; Naguleswaran, Arunasalam; Rehmann, Ruth; Heller, Manfred and Roditi, Isabel

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1553-7366

Publisher:

Public Library of Science

Funders:

[4] Swiss National Science Foundation

Language:

English

Submitter:

Isabel Roditi

Date Deposited:

15 Feb 2021 13:34

Last Modified:

21 Feb 2021 03:02

Publisher DOI:

10.1371/journal.ppat.1009239

PubMed ID:

33493187

BORIS DOI:

10.48350/152206

URI:

https://boris.unibe.ch/id/eprint/152206

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