Acidocalcisomes of eukaryotes
Graphical abstract
Introduction
Since their first description in the protist parasites Trypanosoma brucei [1••] and Trypanosoma cruzi [2], the etiologic agents of African and American trypanosomiasis, respectively, acidocalcisomes have been reported in bacteria [3••, 4••], as well as in many unicellular and multicellular eukaryotes, including humans [5, 6, 7]. Two organelles in mammals, the platelet dense granules [8••] and the mast cell granules [9], have characteristics in common to acidocalcisomes of protists. The biogenesis of these organelles in several protists [10, 11] and mammalian cells [12] involves the function of the adaptor protein 3 (AP-3) complex, as is typical of lysosome-related organelles. Ablation of β3 and δ subunits of the AP-3 complex in T. brucei resulted in disappearance of acidocalcisomes with no alterations in trafficking of different markers to lysosomes [11].
Acidocalcisomes are characterized by their high electron-density when observed by electron microscopy (Figure 1), and by their acidity and high calcium concentration. These characteristics are the reasons for their name and their grouping as one of the acidic calcium stores of the cell [13]. Another peculiarity common to acidocalcisomes of different species is their high content of phosphorus in the form of orthophosphate, pyrophosphate, and short-chain and long-chain polyphosphate [14]. Polyphosphate is a polymer of three to hundreds of orthophosphate monomers linked by high-energy phosphoanhydride bonds similar to those present in ATP [15].
In protists the acidity of acidocalcisomes is maintained by a vacuolar H+-pyrophosphatase (V-H+-PPase), an enzyme also present in the vacuole of plants, and in some species acidocalcisomes have, like the plant vacuole, an additional proton pump, a vacuolar H+-ATPase (V-H+-ATPase). In multicellular organisms lacking a V-H+-PPase, the V-H+-ATPase maintains their acidity [5].
Recent reviews [5, 16] have described the acidocalcisomes from prokaryotes. In this review we will limit our discussion to recent work on acidocalcisomes from eukaryotes.
Section snippets
Acidocalcisomes in protists
A large number of protists possess acidocalcisomes, among them trypanosomatids and Apicomplexan parasites, algae, slime molds, and fungi. We will discuss each of these organisms in the following sections.
Insect, echinoderm and bird eggs
Acidocalcisomes have been found in the yolk of insect [72], echinoderms [73], and bird [74] eggs. They are electron-dense and rich in short chain polyphosphate (chains of less than 100 orthophosphate residues) and cations. In chicken eggs acidocalcisomes are within larger acidic vacuoles forming compound organelles [74]. Acidification is through a V-H+-ATPase in sea urchin and chicken eggs [73, 74]. Although a V-H+-PPase activity was detected in insect eggs [75] there is no genomic information
Mammalian cells
Several lysosome-related organelles of mammalian cells have similarities with acidocalcisomes. The best studied are the platelet dense granules [8••] and the mast cell granules [9]. Human platelet dense granules are electron-dense, possess polyphosphate of about 80 orthophosphate monomers, and cations (Ca2+, K+), and are also known to contain pyrophosphate, ATP, ADP and serotonin. Their acidification is through a V-H+-ATPase [8••]. Polyphosphate is also present in mast cell granules (RBL-2H3
Conclusions
The common properties of acidocalcisomes of different eukaryotes are their high electron-density, their acidic nature, and their high calcium and polyphosphate content. Acidocalcisome acidification is by a V-H+-PPase, by a V-H+-ATPase, or by both. Ca2+ uptake is, at least in protists, by a Ca2+-ATPase, while polyphosphate synthesis and translocation in several protists is by a VTC complex, and by unknown mechanisms in mammalian cells, possibly involving the inositol pyrophosphate pathway. The
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
Research in the authors’ laboratory is funded by the United States National Institutes of Health [grant numbers AI-077538 and AI-108222]. RD is a Barbara and Sanford Orkin/Georgia Research Alliance Eminent Scholar.
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