Proteomic analysis of acidocalcisomes of Trypanosoma brucei uncovers their role in phosphate metabolism, cation homeostasis, and calcium signaling

Abstract

Trypanosoma brucei, the causative agent of African trypanosomiasis, is a unicellular parasite that possesses lysosome-related organelles known as acidocalcisomes. These organelles have been found from bacteria to human cells, and are characterized by their acidic nature and high calcium and polyphosphate (polyP) content. Our proteomic analysis of acidocalcisomes of T. brucei procyclic stages, together with in situ epitope-tagging and immunofluorescence assays with specific antibodies against selected proteins, established the presence of 2 H+ pumps, a vacuolar H+-ATPase and a vacuolar H+-pyrophosphatase, that acidify the organelles as well as of a number of transporters and channels involved in phosphate metabolism, cation uptake and calcium signaling. Together with recent work in other organisms, these results provide direct evidence that acidocalcisomes are especially adapted to accumulate polyP bound to cations and for calcium signaling.