Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsP5 and InsP8 in mammalian cells

Qi, Ji; Shi, Linhui; Zhu, Limei; Chen, Yuanyuan; Zhu, Hong; Cheng, Weiwei; Chen, Alex F.; Fu, Chenglai

doi:10.1007/s12265-023-10427-0

Cited by 8 publications

(1 citation statement)

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“…More nuanced genetic modifications of IP6Ks will also provide key insights into IP6K’s role, not only in the brain, but in other somatic tissues as well. IP6K kinase-inactive, mutant mice could allow us to decipher the roles of IP6K scaffolding interactions versus its enzymatic synthesis of IP7 and IP8 [ 141 ]. Brain-specific KOs of the IP6Ks would provide evidence that the behavioral changes seen in KO mice are specific to changes in the brain.…”

Section: Discussionmentioning

confidence: 99%

The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System

Heitmann,

Barrow

2023

Biomolecules

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Inositol is a unique biological small molecule that can be phosphorylated or even further pyrophosphorylated on each of its six hydroxyl groups. These numerous phosphorylation states of inositol along with the kinases and phosphatases that interconvert them comprise the inositol phosphate signaling pathway. Inositol hexakisphosphate kinases, or IP6Ks, convert the fully mono-phosphorylated inositol to the pyrophosphate 5-IP7 (also denoted IP7). There are three isoforms of IP6K: IP6K1, 2, and 3. Decades of work have established a central role for IP6Ks in cell signaling. Genetic and pharmacologic manipulation of IP6Ks in vivo and in vitro has shown their importance in metabolic disease, chronic kidney disease, insulin signaling, phosphate homeostasis, and numerous other cellular and physiologic processes. In addition to these peripheral processes, a growing body of literature has shown the role of IP6Ks in the central nervous system (CNS). IP6Ks have a key role in synaptic vesicle regulation, Akt/GSK3 signaling, neuronal migration, cell death, autophagy, nuclear translocation, and phosphate homeostasis. IP6Ks’ regulation of these cellular processes has functional implications in vivo in behavior and CNS anatomy.

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Section: Discussionmentioning

confidence: 99%