Abstract
Polyphosphate (polyP), a several billion-year-old biopolymer, is produced in every cell, tissue, and organism studied. Structurally extremely simple, polyP consists of long chains of covalently linked inorganic phosphate groups. We report here the surprising discovery that polyP shows a remarkable efficacy in accelerating amyloid fibril formation. We found that polyP serves as an effective nucleation source for various different amyloid proteins, ranging from bacterial CsgA to human α-synuclein, Aβ1-40/42, and Tau. polyP-associated α-synuclein fibrils show distinct differences in seeding behavior, morphology, and fibril stability compared with fibrils formed in the absence of polyP. In vivo, the amyloid-stimulating and fibril-stabilizing effects of polyP have wide-reaching consequences, increasing the rate of biofilm formation in pathogenic bacteria and mitigating amyloid toxicity in differentiated neuroblastoma cells and C. elegans strains that serve as models for human folding diseases. These results suggest that we have discovered a conserved cytoprotective modifier of amyloidogenic processes.
Copyright © 2016 Elsevier Inc. All rights reserved.
MeSH terms
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Amyloid beta-Peptides / agonists*
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Amyloid beta-Peptides / chemistry
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Amyloid beta-Peptides / genetics
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Amyloid beta-Peptides / metabolism
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Animals
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Animals, Genetically Modified
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Biofilms / drug effects
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Biofilms / growth & development
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Caenorhabditis elegans / drug effects
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism
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Cell Line, Tumor
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Escherichia coli / drug effects
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Escherichia coli Proteins / agonists*
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Escherichia coli Proteins / chemistry
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism
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Gene Expression
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Humans
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Kinetics
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology
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Peptide Fragments / agonists*
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Polyphosphates / chemistry
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Polyphosphates / pharmacology*
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Protein Folding / drug effects
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alpha-Synuclein / agonists*
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alpha-Synuclein / chemistry
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alpha-Synuclein / genetics
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alpha-Synuclein / metabolism
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tau Proteins / agonists*
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tau Proteins / chemistry
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tau Proteins / genetics
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tau Proteins / metabolism
Substances
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Amyloid beta-Peptides
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Escherichia coli Proteins
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MAPT protein, human
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Peptide Fragments
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Polyphosphates
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alpha-Synuclein
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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csgA protein, E coli
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tau Proteins