Abstract
Dynamins and dynamin-like proteins (DLPs) belong to a family of large GTPases involved in membrane remodelling events. These include both fusion and fission processes with different dynamin proteins often having a specialised function within the same organism. Trypanosoma brucei is thought to have only one multifunctional DLP (TbDLP). While this was initially reported to function in mitochondrial division only, an additional role in endocytosis and cytokinesis was later also proposed. Since there are two copies of TbDLP present in the trypanosome genome, we investigated potential functional differences between these two paralogs by re-expressing either protein in a TbDLP RNAi background. These paralogs, called TbDLP1 and TbDLP2, are almost identical bar a few amino acid substitutions. Our results, based on cell lines carrying tagged and RNAi-resistant versions of each protein, show that overexpression of TbDLP1 alone is able to rescue the observed endocytosis and growth defects in the mammalian bloodstream form (BSF) of the parasite. While TbDLP2 shows no rescue in our experiments in BSF, this might also be due to lower expression levels of the protein in this life stage. In contrast, both TbDLP proteins apparently play more complementary roles in the insect procyclic form (PCF) since neither TbDLP1 nor TbDLP2 alone can fully restore wildtype growth and morphology in TbDLP-depleted parasites.
Highlights
Trypanosoma brucei is an important single-celled parasite that causes African trypanosomiasis in humans and the wasting disease nagana in cattle
We started our investigations with the following simple hypothesis: If both highly similar TbDLP proteins fulfil identical functions, why would there be any variation in sequence? Given the extremely rapid endocytosis in bloodstream form (BSF) and the much higher reliance on the process for survival in the context of antigenic variation, upregulation of a TbDLP involved in scission of endocytic vesicles can be envisaged
With the procyclic form (PCF) mitochondrion so much more metabolically active and morphologically complex than its BSF counterpart, the upregulation of machinery involved in mitochondrial division in this life stage seems appropriate
Summary
Trypanosoma brucei is an important single-celled parasite that causes African trypanosomiasis in humans and the wasting disease nagana in cattle. During its development and transmission cycle, T. brucei goes through a variety of morphological and metabolic changes that largely depend on its environment [1]. Whereas the mammalian-dwelling long slender bloodstream form (BSF) flagellates rely solely on glycolysis for energy generation, the main energy source of the insect procyclic form (PCF) are amino acids, such as proline [2]. This metabolic adjustment requires activation of the mitochondrion, with which PCF cells generate most cellular ATP via oxidative phosphorylation, making the organelle more essential for this life cycle.
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