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Unconventional signaling properties of inositol pyrophosphates

Inositol pyrophosphates (PP-InsPs) are messenger molecules in eukaryotic cells, that serve as sensors of phosphate and ATP, among other functions, signaling e.g. through allosteric regulation and posttranslational modifications. This work is structured into two parts, focusing on two different unusual features of these molecules.
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Inositol Pyrophosphates Regulate Inositol Metabolism in Yeast♦ [PDF]

Journal of Biological Chemistry, 2013
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The inositol pyrophosphate 5-InsP₇ drives sodium-potassium pump degradation by relieving an autoinhibitory domain of PI3K p85α. [PDF]

Sci Adv, 2020
Chin AC, Gao Z, Riley AM, Furkert D, Wittwer C, Dutta A, Rojas T, Semenza ER, Felder RA, Pluznick JL, Jessen HJ, Fiedler D, Potter BVL, Snyder SH, Fu C.   +14 more
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Control of XPR1-dependent cellular phosphate efflux by InsP₈ is an exemplar for functionally-exclusive inositol pyrophosphate signaling. [PDF]

Proc Natl Acad Sci U S A, 2020
Li X, Gu C, Hostachy S, Sahu S, Wittwer C, Jessen HJ, Fiedler D, Wang H, Shears SB.   +8 more
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The InsP₇ phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2. [PDF]

J Biol Chem, 2020
Steidle EA, Morrissette VA, Fujimaki K, Chong L, Resnick AC, Capaldi AP, Rolfes RJ.   +6 more
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Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP ₇ metabolism in enteric nervous system

, 2022
Ito M, Fujii N, Kohara S, Hori S, Tanaka M, Wittwer C, Kikuchi K, Iijima T, Kakimoto Y, Hirabayashi K, Kurotaki D, Jessen HJ, Saiardi A, Nagata E.   +13 more
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A two-way switch for inositol pyrophosphate signaling: Evolutionary history and biological significance of a unique, bifunctional kinase/phosphatase. [PDF]

Adv Biol Regul, 2020
Randall TA, Gu C, Li X, Wang H, Shears SB.   +4 more
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Inositol pyrophosphate kinases in health and disease

FEBS Letters
Inositol phosphates (InsPs) are intracellular signaling molecules that are essential for life. Inositol pyrophosphates, a subset of inositol phosphates, are the end products of inositol phosphate metabolism. In mammalian cells, up to 90% of inositol pyrophosphates are 5‐diphosphoinositol 1,2,3,4,6‐pentakisphosphate (5PP‐InsP
Changchang Xing, Chao Wang, Yuanyuan Chen, Weiwei Cheng, Zhaolei Jiang, Alex F. Chen, Chenglai Fu   +6 more
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Enabling Technologies for the Dissection of Inositol Pyrophosphate Physiology

Methods in molecular biology
The diverse chemical structures of inositol pyrophosphates attract growing interest toward this class of small molecule messengers. However, their highly charged nature, the lack of a chromophore or a fluorophore, their close structural relatedness, and the complexity of their metabolism pose serious challenges to inositol pyrophosphates studies. Here,
Adolfo, Saiardi, Henning J, Jessen, Dorothea, Fiedler   +2 more
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Visualizing and Identifying Inositol Pyrophosphate Isomers in Crystallo

Methods in molecular biology
Inositol pyrophosphates (PP-InsPs), which possess functionally significant diphosphate groups, regulate a wide range of biological processes across eukaryotic organisms. The presence and isomeric diversity of PP-InsPs suggest potential biological relevance and enable these molecules to serve as versatile regulators.
Guangning, Zong, Huanchen, Wang
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