Table Of ContentTatiana Kulakovskaya · Evgeny Pavlov
Elena N. Dedkova Editors
Inorganic
Polyphosphates
in Eukaryotic
Cells
Inorganic Polyphosphates
in Eukaryotic Cells
Tatiana Kulakovskaya (cid:129) Evgeny Pavlov
Elena N. Dedkova
Editors
Inorganic Polyphosphates
in Eukaryotic Cells
Editors
Tatiana Kulakovskaya Elena N. Dedkova
Laboratory of Regulation of Biochemical Department of Pharmacology
Processes University of California
Skryabin Institute of Biochemistry and Davis , CA
Physiology of Microorganisms USA
Russian Academy of Sciences
Pushchino , Russia
Evgeny Pavlov
NYU College of Dentistry
New York , New York
USA
ISBN 978-3-319-41071-5 ISBN 978-3-319-41073-9 (eBook)
DOI 10.1007/978-3-319-41073-9
Library of Congress Control Number: 2016957150
© Springer International Publishing Switzerland 2016
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Pref ace
I norganic polyphosphate is a biological polymer made of many orthophosphates
linked together by phosphoanhydride bonds similar to ones found in ATP. polyP is
a unique macromolecule that can spontaneously form in nonliving nature and can
also be enzymatically produced by living organisms. Over the past few decades, a
number of exciting hypotheses regarding the role of polyP in nature have been gen-
erated. These range from the concept that polyP can be a prebiotic molecule that
was at the origin to living organisms to the concept that polyP can serve as a storage
of biological fuel alternative to ATP. Despite its discovery over a century ago, the
molecular mechanisms of polyP actions in living organisms remain poorly under-
stood. In fact, most of current knowledge about biological roles of polyP comes
from the studies of bacterial organisms and lower eukaryotes with very little studies
of higher eukaryotes. One of the central unresolved questions in polyP research is
about the relationship between its roles in different organisms. Is polyP indeed a
“molecular fossil” which has a role in higher organisms that progressively dimin-
ished over the evolution, or is polyP a central player in various biochemical pro-
cesses throughout all kingdoms of life? Although at present it is impossible to
defi nitively answer this question, recent discoveries regarding the roles of polyP
support the idea that polyP maintains an important role in all living organisms
including humans. This book presents a collection of chapters dedicated to the cur-
rent research in the fi eld of eukaryotic polyP. It is divided in two sections with the
fi rst focusing on polyP function in simple organisms and the second on polyP func-
tion in higher organisms. This book is intended to bring together the perspectives of
scientists working in various fi elds of life sciences, which we believe will provide a
broad overview of the current state of the fi eld and help to better understand current
achievements and challenges.
W e would like to express the gratitude to all authors who contributed to this book
for their cooperation, help, and patience.
Pushchino , Russia Tatiana Kulakovskaya
New York, NY , USA Evgeny Pavlov
Davis , CA , USA Elena N. Dedkova
v
Contents
Part I Lower Eukaryotes
1 The Role of Inorganic Polyphosphates in Stress Response
and Regulation of Enzyme Activities in Yeast . . . . . . . . . . . . . . . . . . . . . . 3
Tatiana Kulakovskaya , Lubov Ryasanova , Vladimir Dmitriev ,
and Anton Zvonarev
2 Yeast Polyphosphatases PPX1 and PPN1: Properties,
Functions, and Localization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Nadeshda Andreeva , Lidia Lichko , Ludmila Trilisenko ,
Ivan V. Kulakovskiy , and Tatiana Kulakovskaya
3 Polyphosphate Storage and Function in Acidocalcisomes . . . . . . . . . . . 35
Roberto Docampo
4 Inorganic Polyphosphates in Mycorrhiza . . . . . . . . . . . . . . . . . . . . . . . . . 49
Tatsuhiro Ezawa , Chiharu Tani , Nowaki Hijikata ,
and Yusuke Kikuchi
5 Functions of Inositol Polyphosphate and Inorganic
Polyphosphate in Yeast and Amoeba . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Adolfo Saiardi
Part II Higher Eukaryotes
6 Methods of Inorganic Polyphosphate (PolyP) Assay
in Higher Eukaryotic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Maria E. Solesio and Evgeny V. Pavlov
7 Inorganic Polyphosphates in the Mitochondria
of Mammalian Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Lea K. Seidlmayer and Elena N. Dedkova
8 Role of Inorganic Polyphosphate in the Cells
of the Mammalian Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Artyom Y. Baev , Plamena R. Angelova , and Andrey Y. Abramov
vii
viii Contents
9 Inorganic Polyphosphate Functions and Metabolism
in Insects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Fabio Mendonça Gomes , I. B. Ramos , H. Araujo , K. Miranda ,
and E. A. Ednildo
10 Inorganic Polyphosphate and Its Chain- Length
Dependency in Tissue Regeneration
Including Bone Remodeling and Teeth Whitening . . . . . . . . . . . . . . . . 139
Toshikazu Shiba
11 Inorganic Polyphosphate in Blood Coagulation. . . . . . . . . . . . . . . . . . . 159
Stephanie A. Smith and James H. Morrissey
12 Influence of Condensed Phosphates on the Physical Chemistry
of Calcium Phosphate Solids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Sidney Omelon and Wouter Habraken
13 Inorganic Polyphosphate Is an Essential Structural
and Functional Component of the Mammalian Ion
Channel TRPM8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Eleonora Zakharian
14 Inorganic Polyphosphate in Tissue Engineering . . . . . . . . . . . . . . . . . . 217
Rahul Gawri , Jean-Philippe St-Pierre , Robert Pilliar ,
Marc Grynpas , and Rita A. Kandel
Conclusion: Evolution of the Polyphosphate Role in Eukaryotes . . . . . . . . 241
Part I
Lower Eukaryotes
1
The Role of Inorganic Polyphosphates
in Stress Response and Regulation
of Enzyme Activities in Yeast
Tatiana Kulakovskaya , Lubov Ryasanova ,
Vladimir Dmitriev , and Anton Zvonarev
Abstract
Inorganic polyphosphates (polyPs) are multifunctional compounds involved in adap-
tation of microorganisms to stress. In yeast, polyPs serve a reserve of phosphorus that
is consumed by cells with phosphate defi ciency. Under phosphate excess, polyP bio-
synthesis regulates the intracellular phosphate concentration. PolyPs accumulate
under conditions of growth suppression under nitrogen starvation and heavy metal
toxic stress, and also upon the adaptation of yeast to a hydrophobic carbon source.
The participation of polyPs in the regulation of enzyme activities is discussed.
1.1 Introduction
I norganic polyphosphates (polyPs) are linear polymers containing a few to several
hundred orthophosphate residues linked by energy-rich phosphoanhydride bonds
(Fig. 1 .1 ). Until recently they were considered molecular fossils, ATP precursors in
evolution, and a phosphorus storage mechanism in microorganisms. Igor Kulaev, a
pioneer in polyP biochemistry, suggested multiple roles for these polymers in the
regulation of cellular processes because of the ability to form complexes with metal
ions, proteins, and RNA (Kulaev 1 979) . The interaction of negatively charged pol-
yPs with anionic biopolymers, such as poly-beta hydroxybutyrate (Reusch 1992 )
and probably RNA (Kulaev 1 979 ), is mediated by divalent metal cations.
T. Kulakovskaya (*)
Laboratory of Regulation of Biochemical Processes , Skryabin Institute of Biochemistry and
Physiology of Microorganisms, Russian Academy of Sciences , Pushchino ,
Moscow Region 142290 , Russia
e-mail: [email protected]
L. Ryasanova (cid:129) V. Dmitriev (cid:129) A. Zvonarev
Skryabin Institute of Biochemistry and Physiology of Microorganisms,
Russian Academy of Sciences, Pushchino , Moscow Region 142290 , Russia
© Springer International Publishing Switzerland 2016 3
T. Kulakovskaya et al. (eds.), Inorganic Polyphosphates in Eukaryotic Cells,
DOI 10.1007/978-3-319-41073-9_1
4 T. Kulakovskaya et al.
Fig. 1.1 Structure of
linear inorganic
polyphosphate (polyP)
The excellent studies of Arthur Kornberg and co-workers demonstrated the
essential role of polyPs in the switching of gene expression and in cell survival in
the stationary phase and under stress (Kornberg 1 995; Rao et al. 2009) . PolyP and
polyphosphate kinase participate in induction of the synthesis of RpoS, an RNA-
polymerase subunit in bacteria that is responsible for expression of the genes
involved in the stationary phase and adaptation to stress; it is also involved in bacte-
rial cell motility, biofi lm formation, and virulence (Rao et al. 2 009 ).
The adaptation of E scherichia coli to amino acid starvation is a remarkable exam-
ple of polyP involvement in the response to stress (Rao et al. 2009 ). This process is
mediated by guanosine 5′-triphosphate, 3′-diphosphate (pppGpp) and guanosine
5′-diphosphate, 3′-diphosphate (ppGpp), the so-called alarmones. These compounds
enhance the expression of many stress-induced genes (Magnusson et al. 2 005 ;
Sharma and Chatterji 2 010 ). The increase of concentrations of (p)ppGpp in E . coli
cells enhances the degradation of polyPs by polyphosphatases ppx and gppA (Kuroda
2006) . The gppA enzyme also catalyzes the degradation of p(ppGpp) (Keasling et al.
1993 ). As a result, the polyP content in E. coli increases many fold under amino acid
starvation. PolyP forms a complex with ATP-dependent Lon proteinase and increases
its activity (Kuroda 2 006) . These polyPs, with an average chain length of 65–700
phosphate residues, bind up to four Lon molecules per one polyP chain, and such a
complex is responsible for the proteolysis of ribosomal proteins (Kuroda 2 006 ). The
resulting free amino acids are used for biosynthesis of inducible amino acid trans-
porters and enzymes of amino acid biosynthesis.
The mechanisms of polyP participation in stress response in eukaryotic microor-
ganisms are not yet well understood. However, many facts suggest the involvement
of polyP in the adaptive mechanisms in fungi:
(cid:129) The polyP content and chain length are strongly dependent on the growth stage
and conditions
(cid:129) P olyP was found in vacuoles, cytoplasm, cell wall, nuclei, and mitochondria by
both subcellular fractionation methods and various microscopic techniques
(cid:129) The cell compartments possess specifi c enzymes of polyP metabolism, differ-
ently affecting by environmental conditions
T his chapter considers changes in polyP content and chain length under various
stresses and the involvement of polyP in the regulation of enzyme activities in yeast.
1.2 P Limitation and Excess
i
PolyP content in the cells of S accharomyces cerevisiae strongly depends on the culture
medium composition and the growth stage (Vagabov et al. 1 998 , 2000) . The polyP pool
of yeast is heterogenic: traditionally fi ve polyP fractions were isolated from S . cerevisiae
