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Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

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Abstract

The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P 3] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P 3. These enzymes terminate the signal to release Ca2+ from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P 4]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties of intracellular signals, leading to the formation of persistent molecular memories.

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Abbreviations

ACPD:

1-Aminocyclopentane-trans-1, 3-dicarboxylic acid

AMPA:

Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

BCR:

B cell receptor

CaM:

Calmodulin

CamKII:

Ca2+/calmodulin-dependent kinase II

ERK:

Extracellular signal-regulated kinase

ER:

Endoplasmic reticulum

IP:

Inositol phosphate

InsP 3 :

Inositol trisphosphate [Ins(1,4,5)P 3]

InsP 4 :

Inositol tetrakisphosphate [Ins(1,3,4,5)P 4]

IPK:

Inositol polyphosphate kinase

F-actin:

Filamentous actin

INPP5A:

Inositol polyphosphate 5-kinase type 1

IPMK:

Inositol polyphosphate multikinase

ITK:

Interleukin-2 inducible T cell tyrosine kinase

ITPK:

Inositol trisphosphate 3-kinase

ITPR:

Inositol trisphosphate receptor

LTP:

Long term potentiation

NMDA:

N-methyl-d-aspartate

PH:

Pleckstrin homology

PI3K:

Phosphatidylinositol lipid 3-kinase

SOC:

Stores operated channel

TCR:

T cell receptor

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Acknowledgments

Thanks to Pavel Gusev for critical reading and Gudrun Ihrke for assistance with the figures. The author is supported by USU grants RO75NX and RO75PJ, and a Research Starter grant from the PhRMA Foundation. The opinions or assertions contained herein are the private ones of the author and are not to be construed as official or reflecting the view of the Department of Defense or the Uniformed Services University.

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    Michael J. Schell

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Schell, M.J. Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling. Cell. Mol. Life Sci. 67, 1755–1778 (2010). https://doi.org/10.1007/s00018-009-0238-5

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