Trypanosoma brucei Vacuolar Transporter Chaperone 4 (TbVtc4) Is an Acidocalcisome Polyphosphate Kinase Required for in Vivo Infection

Lander, Noelia; Ulrich, Paul N.; Docampo, Roberto

doi:10.1074/jbc.m113.518993

Cited by 72 publications

(98 citation statements)

References 49 publications

(38 reference statements)

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“…Clearly, understanding the regulation of polyP metabolism is instrumental to appreciating phosphate homeostasis. shows a 35% decrease in short chain polyP species with no significant changes in the long chain polyP [71]. Therefore another uncharacterized enzyme able to synthesize polyP in T.…”

Section: Inorganic Polyphosphate As a Eukaryote Phosphate Buffermentioning

confidence: 99%

Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective

Azevedo

Saiardi

2017

Trends in Biochemical Sciences

133

129

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Section: Inorganic Polyphosphate As a Eukaryote Phosphate Buffermentioning

confidence: 99%

Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective

Azevedo

Saiardi

2017

Trends in Biochemical Sciences

133

129

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“…PolyP is important in detoxification of heavy metals and in counteracting alkaline and osmotic stress (Keasling, 1997;Pick and Weiss, 1991;Rohloff and Docampo, 2008). In addition, infectivity and persistence of prokaryotic and eukaryotic parasites depend on their polyP stores (Galizzi et al, 2013;Kim et al, 2002;Lander et al, 2013). The ability of polyP to stabilize proteins and act as a chaperone increases stress tolerance of cells (Azevedo et al, 2015;Dahl et al, 2015;Gray et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Ppn2, a novel Zn2+-dependent polyphosphatase in the acidocalcisome-like yeast vacuole

Gerasimaitė

Mayer

2017

Journal of Cell Science

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Acidocalcisome-like organelles are found in all kingdoms of life. Many of their functions, such as the accumulation and storage of metal ions, nitrogen and phosphate, the activation of blood clotting and inflammation, depend on the controlled synthesis and turnover of polyphosphate ( polyP), a polymer of inorganic phosphate linked by phosphoric anhydride bonds. The exploration of the role of acidocalcisomes in metabolism and physiology requires the manipulation of polyP turnover, yet the complete set of proteins responsible for this turnover is unknown. Here, we identify a novel type of polyphosphatase operating in the acidocalcisome-like vacuoles of the yeast Saccharomyces cerevisiae, which we called Ppn2. Ppn2 belongs to the PPP-superfamily of metallophosphatases, is activated by Zn 2+ ions and exclusively shows endopolyphosphatase activity. It is sorted to vacuoles via the multivesicular body pathway. Together with Ppn1, Ppn2 is responsible for a substantial fraction of polyphosphatase activity that is necessary to mobilize polyP stores, for example in response to phosphate scarcity. This finding opens the way to manipulating polyP metabolism more profoundly and deciphering its roles in phosphate and energy homeostasis, as well as in signaling.

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“…The synthesis, enzymology, and role of polyP are best characterized in the bacteria Escherichia coli (2). However, polyP is also present in archaea (3), eukaryotes (4), and human cells (5). Whilst polyP is present in virtually all cellular compartments (6), it accumulates in acidocalcisomes, organelles common to bacteria and mammalian cells (7).…”

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confidence: 99%

Developmental accumulation of inorganic polyphosphate affects germination and energetic metabolism in Dictyostelium discoideum

Livermore

Chubb

Saiardi

2016

Proc. Natl. Acad. Sci. U.S.A.

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Inorganic polyphosphate (polyP) is composed of linear chains of phosphate groups linked by high-energy phosphoanhydride bonds. However, this simple, ubiquitous molecule remains poorly understood. The use of nonstandardized analytical methods has contributed to this lack of clarity. By using improved polyacrylamide gel electrophoresis we were able to visualize polyP extracted from Dictyostelium discoideum. We established that polyP is undetectable in cells lacking the polyphosphate kinase (DdPpk1). Generation of this ppk1 null strain revealed that polyP is important for the general fitness of the amoebae with the mutant strain displaying a substantial growth defect. We discovered an unprecedented accumulation of polyP during the developmental program, with polyP increasing more than 100-fold. The failure of ppk1 spores to accumulate polyP results in a germination defect. These phenotypes are underpinned by the ability of polyP to regulate basic energetic metabolism, demonstrated by a 2.5-fold decrease in the level of ATP in vegetative ppk1. Finally, the lack of polyP during the development of ppk1 mutant cells is partially offset by an increase of both ATP and inositol pyrophosphates, evidence for a model in which there is a functional interplay between inositol pyrophosphates, ATP, and polyP.inorganic polyphosphate | phosphate | metabolism | inositol pyrophosphate | mitochondria T he simplest biological polymer is inorganic polyphosphate (polyP), which consists of a linear chain of phosphates linked by high-energy phosphoanhydride bonds (1). Regardless of its origin, polyP is ubiquitously present in today's living organisms. The synthesis, enzymology, and role of polyP are best characterized in the bacteria Escherichia coli (2). However, polyP is also present in archaea (3), eukaryotes (4), and human cells (5). Whilst polyP is present in virtually all cellular compartments (6), it accumulates in acidocalcisomes, organelles common to bacteria and mammalian cells (7).PolyP has been implicated in a range of cellular processes over recent years, but its most basic proposed function is to act as a buffer for the level of free phosphate (8). Phosphate buffering is essential for general metabolism, and the synthesis or degradation of polyP is able to safeguard the level of free phosphate in cells. In addition, the polyanionic nature of polyP makes it a strong chelator of bivalent cations; thus polyP plays a key role in cation homeostasis. The chelation of calcium by polyP might even play a role as a calcium sink, regulating calcium signaling (8). Besides these common roles, many specific functions have been attributed to polyP in eukaryotes (see reviews in refs. 9-11). Recently its ability to function as a protein-folding chaperone (12) and to drive a newly discovered posttranslational protein modification, protein polyphosphorylation (13), have provided further insight into the mechanism of action of this simple polymer.Little is known about the synthesis or metabolism of polyP in eukaryotes. The yeast Saccharomyces c...

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Trypanosoma brucei Vacuolar Transporter Chaperone 4 (TbVtc4) Is an Acidocalcisome Polyphosphate Kinase Required for in Vivo Infection

Cited by 72 publications

References 49 publications

Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective

Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective

Ppn2, a novel Zn2+-dependent polyphosphatase in the acidocalcisome-like yeast vacuole

Developmental accumulation of inorganic polyphosphate affects germination and energetic metabolism in Dictyostelium discoideum

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