Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

Abstract

Inositol pyrophosphates (PP-IPs) are a class of energy-rich
signalling molecules found in all eukaryotic cells. These are derivatives
of inositol that contain one or more diphosphate (or pyrophosphate)
groups in addition to monophosphates. The more abundant and
best studied PP-IPs are diphosphoinositol pentakisphosphate (IP7) and
bis-diphosphoinositol tetrakisphosphate (IP8). These molecules can
influence protein function by two mechanisms: binding and pyrophosphorylation.
The former involves the specific interaction of a particular
inositol pyrophosphate with a binding site on a protein, while the latter is
a unique attribute of inositol pyrophosphates, wherein the β-phosphate
moiety is transferred from a PP-IP to a pre-phosphorylated serine residue
in a protein to generate pyrophosphoserine. Both these events can
result in changes in the target protein’s activity, localisation or its interaction
with other partners. As a consequence of their ubiquitous presence
in all eukaryotic organisms and all cell types examined till date, and their
ability to modify protein function, PP-IPs have been found to participate
in a wide range of metabolic, developmental, and signalling pathways.
This review highlights many of the known functions of PP-IPs in the context
of their temporal and spatial distribution in eukaryotic cells.