Inorganic Polyphosphate Is an Essential Structural and Functional Component of the Mammalian Ion Channel TRPM8
Inorganic polyphosphate (polyP) is the largest inorganic macromolecule known in living organisms. The presence of polyP in the volcanic environment is indicative of its essential contribution to prebiotic evolution. On the other hand, the ubiquitous expre
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Eleonora Zakharian
Abstract
Inorganic polyphosphate (polyP) is the largest inorganic macromolecule known in living organisms. The presence of polyP in the volcanic environment is indicative of its essential contribution to prebiotic evolution. On the other hand, the ubiquitous expression of polyP in higher eukaryotes suggests its important physiologic roles. Therefore, a question of whether polyP is a “molecular fossil” that can be viewed as a trace material from an evolutionary perspective, or, perhaps, polyP is implicated in the critical physiological processes, is yet to be determined. However, not only the ubiquitous presence of this polymer at all levels of the living hierarchy but also its expression pattern in the critical life organs like the brain, heart, liver, etc. indicates its indispensible physiological function. In this chapter, I review one of the most beautiful functions of polyP, its contribution to the formation of ion channels. This role of polyP is conditioned by its physicochemical nature. This to be said that polyP is a highly negatively charged polymorphic homopolymer, composed of tens or hundreds of phosphate residues linked by high-energy phosphoanhydride bonds. The multiple charges along the polyP’s backbone create a high capacity for ion exchange with a preference for binding multivalent cations, attributed to their higher binding energies. For instance, Ca2+ and polyP thus make stable salt formation, which can subsequently be solubilized by another mysterious polymer, polyhydroxybutyrate (PHB). PHB is a homopolymer, comprised of ketone bodies β-hydroxybutyrate. Incorporation of the PHB-polyP-Ca2+ complex into the membrane creates an ideally Ca2+-selective channel, where the cations move along the polymers, when driving force in the form of membrane potential or ion gradient is applied. The nuances of this polymeric channel formation and its association with ion channel proteins are the focus of this chapter. E. Zakharian Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, 1 Illini Dr., Peoria, IL 61605, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 T. Kulakovskaya et al. (eds.), Inorganic Polyphosphates in Eukaryotic Cells, DOI 10.1007/978-3-319-41073-9_13
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E. Zakharian
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13.1
Introduction
Inorganic polyphosphate (polyP) is the largest inorganic macromolecule known in living organisms. PolyP is a linear homopolymer consisting of orthophosphate residues linked by high-energy phosphoanhydride bonds (Fig. 13.1) (Kornberg 1995). In mammals the polymers of polyP vary greatly in their length in a tissue- or organspecific manner (Gabel and Thomas 1971). The diversity in polyP amounts and lengths in various tissues suggests multiplicity of specific roles amended by this polyanion (Kumble and Kornberg 1995), although many of them yet remain elusive. The most anticipated polyP contribution would be accounted for its high-energy bonds and highly negative charge density carried by the polymer. Indeed, the m
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