scholarly journals Inositol Trisphosphate Kinase and Diphosphoinositol Pentakisphosphate Kinase Enzymes Constitute the Inositol Pyrophosphate Synthesis Pathway in Plants

2019 ◽  
Author(s):  
Olusegun Adepoju ◽  
Sarah P. Williams ◽  
Branch Craige ◽  
Caitlin A. Cridland ◽  
Amanda K. Sharpe ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
High Energy ◽  
Signaling Molecules ◽  
Loss Of Function ◽  
Inositol Pyrophosphate ◽  
Overexpression Line ◽  
Inositol Pyrophosphates ◽  
Intracellular Signaling Molecules ◽  
Inositol Ring

ABSTRACTInositol pyrophosphates (PP-InsPs) are an emerging class of “high-energy” intracellular signaling molecules containing one or two diphosphate groups attached to an inositol ring, with suggested roles in bioenergetic homeostasis and inorganic phosphate (Pi) sensing. Information regarding the biosynthesis of these unique class of signaling molecules in plants is scarce, however the enzymes responsible for their biosynthesis in other eukaryotes have been well described. Here we report the characterization of the two Arabidopsis VIP kinase domains, a newly discovered activity of the Arabidopsis ITPK1 and ITPK2 enzymes, and the subcellular localization of the enzymes involved in the synthesis of InsP6and PP-InsPs. Our data indicate that AtVIP1-KD and AtVIP2-KD act primarily as 1PP-specific Diphosphoinositol Pentakisphosphate Kinases (PPIP5) Kinases. The AtITPK enzymes, in contrast, can function as InsP6kinases, and thus are the missing enzyme in the plant PP-InsP synthesis pathway. Together, these enzyme classes can function in plants to produce PP-InsPs, which have been implicated in signal transduction and Pisensing pathways. We measured a higher InsP7level (increased InsP7/InsP8ratio) invip1/vip2double loss-of-function mutants, and an accumulation of InsP8(decreased InsP7/InsP8ratio) in the 35S:VIP2overexpression line relative to wild-type plants. We also report that enzymes involved in the synthesis of InsPs and PP-InsPs accumulate within the nucleus and cytoplasm of plant cells. Our work defines a molecular basis for understanding how plants synthesize PP-InsPs which is crucial for determining the roles of these signaling molecules in processes such as Pisensing.SIGNIFICANCE STATEMENTInositol pyrophosphate signaling molecules are of agronomic importance as they can control complex responses to the limited nutrient, phosphate. This work fills in the missing steps in the inositol pyrophosphate synthesis pathway and points to a role for these molecules in the plant cell nucleus. This is an important advance that can help us design future strategies to increase phosphate efficiency in plants.

scholarly journals Can Inositol Pyrophosphates Inform Strategies for Developing Low Phytate Crops?

Plants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 115 ◽  
Author(s):  
Catherine Freed ◽  
Olusegun Adepoju ◽  
Glenda Gillaspy
Keyword(s):  
Intracellular Signaling ◽  
Plant Hormone ◽  
High Energy ◽  
Signaling Molecules ◽  
New Class ◽  
Phosphate Sensing ◽  
Inositol Pyrophosphates ◽  
Intracellular Signaling Molecules ◽  
Inositol Ring ◽  
Phosphate Groups

Inositol pyrophosphates (PP-InsPs) are an emerging class of “high-energy” intracellular signaling molecules, containing one or two diphosphate groups attached to an inositol ring, that are connected with phosphate sensing, jasmonate signaling, and inositol hexakisphosphate (InsP6) storage in plants. While information regarding this new class of signaling molecules in plants is scarce, the enzymes responsible for their synthesis have recently been elucidated. This review focuses on InsP6 synthesis and its conversion into PP-InsPs, containing seven and eight phosphate groups (InsP7 and InsP8). These steps involve two types of enzymes: the ITPKs that phosphorylate InsP6 to InsP7, and the PPIP5Ks that phosphorylate InsP7 to InsP8. This review also considers the potential roles of PP-InsPs in plant hormone and inorganic phosphate (Pi) signaling, along with an emerging role in bioenergetic homeostasis. PP-InsP synthesis and signaling are important for plant breeders to consider when developing strategies that reduce InsP6 in plants, as this will likely also reduce PP-InsPs. Thus, this review is primarily intended to bridge the gap between the basic science aspects of PP-InsP synthesis/signaling and breeding/engineering strategies to fortify foods by reducing InsP6.

Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gleb Nikolaevich Zyuz’kov ◽  
Larisa Arkad`evna Miroshnichenko ◽  
Elena Vladislavovna Simanina ◽  
Larisa Alexandrovna Stavrova ◽  
Tatyana Yur`evna Polykova
Keyword(s):  
Stem Cells ◽  
Alcohol Abuse ◽  
Intracellular Signaling ◽  
Signaling Molecules ◽  
Growth Potential ◽  
Nerve Tissue ◽  
Intracellular Signaling Molecules

Abstract Objectives The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo. Methods In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used. Results Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy). Conclusions The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse.

scholarly journals Asp1 Bifunctional Activity Modulates Spindle Function via Controlling Cellular Inositol Pyrophosphate Levels inSchizosaccharomyces pombe

2018 ◽  
Vol 38 (9) ◽  
pp. e00047-18 ◽  
Author(s):  
Marina Pascual-Ortiz ◽  
Adolfo Saiardi ◽  
Eva Walla ◽  
Visnja Jakopec ◽  
Natascha A. Künzel ◽  
...  
Keyword(s):  
High Energy ◽  
Loss Of Function ◽  
Content Type ◽  
Inositol Pyrophosphate ◽  
Daughter Cells ◽  
Chromosome Transmission ◽  
Microtubule Stability ◽  
Mitochondrial Distribution ◽  
Spindle Function

ABSTRACTThe generation of two daughter cells with the same genetic information requires error-free chromosome segregation during mitosis. Chromosome transmission fidelity is dependent on spindle structure/function, which requires Asp1 in the fission yeastSchizosaccharomyces pombe. Asp1 belongs to the diphosphoinositol pentakisphosphate kinase (PPIP5K)/Vip1 family which generates high-energy inositol pyrophosphate (IPP) molecules. Here, we show that Asp1 is a bifunctional enzymein vivo: Asp1 kinase generates specific IPPs which are the substrates of the Asp1 pyrophosphatase. Intracellular levels of these IPPs directly correlate with microtubule stability: pyrophosphatase loss-of-function mutants raised Asp1-made IPP levels 2-fold, thus increasing microtubule stability, while overexpression of the pyrophosphatase decreased microtubule stability. Absence of Asp1-generated IPPs resulted in an aberrant, increased spindle association of theS. pombekinesin-5 family member Cut7, which led to spindle collapse. Thus, chromosome transmission is controlled via intracellular IPP levels. Intriguingly, identification of the mitochondrion-associated Met10 protein as the first pyrophosphatase inhibitor revealed that IPPs also regulate mitochondrial distribution.

Inositol pyrophosphates: between signalling and metabolism

2013 ◽  
Vol 452 (3) ◽  
pp. 369-379 ◽  
Author(s):  
Miranda S. C. Wilson ◽  
Thomas M. Livermore ◽  
Adolfo Saiardi
Keyword(s):  
High Energy ◽  
Present Review ◽  
Cellular Functions ◽  
Yeast Saccharomyces Cerevisiae ◽  
Diverse Range ◽  
Inositol Pyrophosphate ◽  
Atp Production ◽  
Recent Innovation ◽  
The Social ◽  
Inositol Pyrophosphates

The present review will explore the insights gained into inositol pyrophosphates in the 20 years since their discovery in 1993. These molecules are defined by the presence of the characteristic ‘high energy’ pyrophosphate moiety and can be found ubiquitously in eukaryotic cells. The enzymes that synthesize them are similarly well distributed and can be found encoded in any eukaryote genome. Rapid progress has been made in characterizing inositol pyrophosphate metabolism and they have been linked to a surprisingly diverse range of cellular functions. Two decades of work is now beginning to present a view of inositol pyrophosphates as fundamental, conserved and highly important agents in the regulation of cellular homoeostasis. In particular it is emerging that energy metabolism, and thus ATP production, is closely regulated by these molecules. Much of the early work on these molecules was performed in the yeast Saccharomyces cerevisiae and the social amoeba Dictyostelium discoideum, but the development of mouse knockouts for IP6K1 and IP6K2 [IP6K is IP6 (inositol hexakisphosphate) kinase] in the last 5 years has provided very welcome tools to better understand the physiological roles of inositol pyrophosphates. Another recent innovation has been the use of gel electrophoresis to detect and purify inositol pyrophosphates. Despite the advances that have been made, many aspects of inositol pyrophosphate biology remain far from clear. By evaluating the literature, the present review hopes to promote further research in this absorbing area of biology.

scholarly journals Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules

2006 ◽  
Vol 103 (9) ◽  
pp. 3322-3326 ◽  
Author(s):  
F. Weerkamp ◽  
M. R. M. Baert ◽  
B. A. E. Naber ◽  
E. E. L. Koster ◽  
E. F. E. de Haas ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Differential Expression ◽  
Intracellular Signaling ◽  
Signaling Molecules ◽  
Intracellular Signaling Molecules
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